Akiyama, Masashi; Choate, Keith; Hernández-Martín, Ángela; Aldwin-Easton, Mandy; Bodemer, Christine; Gostyński, Antoni; Hovnanian, Alain; Ishida-Yamamoto, Akemi; Malovitski, Kiril; O'Toole, Edel A; Paller, Amy S; Schmuth, Matthias; Schwartz, Janice; Sprecher, Eli; Teng, Joyce M C; Tournier, Céline Granier; Mazereeuw-Hautier, Juliette; Tadini, Gianluca; Fischer, Judith Nonsyndromic epidermal differentiation disorders: a new classification toward pathogenesis-based therapy Journal Article In: Br J Dermatol, vol. 193, no. 4, pp. 619–641, 2025, ISSN: 1365-2133. @article{pmid40308026,
title = {Nonsyndromic epidermal differentiation disorders: a new classification toward pathogenesis-based therapy},
author = {Masashi Akiyama and Keith Choate and Ángela Hernández-Martín and Mandy Aldwin-Easton and Christine Bodemer and Antoni Gostyński and Alain Hovnanian and Akemi Ishida-Yamamoto and Kiril Malovitski and Edel A O'Toole and Amy S Paller and Matthias Schmuth and Janice Schwartz and Eli Sprecher and Joyce M C Teng and Céline Granier Tournier and Juliette Mazereeuw-Hautier and Gianluca Tadini and Judith Fischer},
doi = {10.1093/bjd/ljaf154},
issn = {1365-2133},
year = {2025},
date = {2025-09-01},
urldate = {2025-09-01},
journal = {Br J Dermatol},
volume = {193},
number = {4},
pages = {619--641},
abstract = {Epidermal differentiation disorders (EDDs) encompass inherited conditions characterized by abnormal epidermal differentiation, including nonsyndromic and syndromic subtypes with more extensive cutaneous involvement or palmoplantar keratoderma. Nonsyndromic EDDs (nEDDs) are defined as disorders that primarily affect large areas of skin and adnexal structures without alterations in extracutaneous tissues resulting from the underlying genetic change. To facilitate the development of targeted therapies and to provide clinicians with clearer therapeutic guidance, we have developed a new nomenclature for EDDs that includes the causative altered gene and the nEDD subgroup designation, sometimes with a clinical or histological descriptor or acronym. Historically, many nEDDs have been named on the basis of phenotypic characteristics or associations that are now considered outdated or inappropriate. For example, the term 'harlequin ichthyosis' evokes potentially stigmatizing images. Similarly, the word 'ichthyosis' is derived from the Greek ichthys, meaning fish, and the Greek hystrix, meaning porcupine, further emphasizing the need to abandon derogatory terminology. As a result, the clinical relevance of the previous classification, which included eponymous and/or descriptive titles, has diminished. In the new, gene-based classification, old terms considered pejorative, such as ichthyosis, vulgaris, hystrix and harlequin have been eliminated and eponyms have been replaced. Among the 53 genetically distinct nEDDs are conditions formerly known as autosomal recessive congenital ichthyosis, erythrokeratodermia variabilis et progressiva, Hailey-Hailey disease and Darier-White disease. This review outlines the updated nomenclature and classifications of nEDDs, linked to detailed clinical descriptions and representative photographs to guide practitioners.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Epidermal differentiation disorders (EDDs) encompass inherited conditions characterized by abnormal epidermal differentiation, including nonsyndromic and syndromic subtypes with more extensive cutaneous involvement or palmoplantar keratoderma. Nonsyndromic EDDs (nEDDs) are defined as disorders that primarily affect large areas of skin and adnexal structures without alterations in extracutaneous tissues resulting from the underlying genetic change. To facilitate the development of targeted therapies and to provide clinicians with clearer therapeutic guidance, we have developed a new nomenclature for EDDs that includes the causative altered gene and the nEDD subgroup designation, sometimes with a clinical or histological descriptor or acronym. Historically, many nEDDs have been named on the basis of phenotypic characteristics or associations that are now considered outdated or inappropriate. For example, the term 'harlequin ichthyosis' evokes potentially stigmatizing images. Similarly, the word 'ichthyosis' is derived from the Greek ichthys, meaning fish, and the Greek hystrix, meaning porcupine, further emphasizing the need to abandon derogatory terminology. As a result, the clinical relevance of the previous classification, which included eponymous and/or descriptive titles, has diminished. In the new, gene-based classification, old terms considered pejorative, such as ichthyosis, vulgaris, hystrix and harlequin have been eliminated and eponyms have been replaced. Among the 53 genetically distinct nEDDs are conditions formerly known as autosomal recessive congenital ichthyosis, erythrokeratodermia variabilis et progressiva, Hailey-Hailey disease and Darier-White disease. This review outlines the updated nomenclature and classifications of nEDDs, linked to detailed clinical descriptions and representative photographs to guide practitioners. |
Collercandy, Nived; Vellas, Camille; Nayrac, Manon; Requena, Mary; Richarme, Thomas; Iscache, Anne-Laure; Latour, Justine; Barange, Karl; Alric, Laurent; Martin-Blondel, Guillaume; Serino, Matteo; Izopet, Jacques; Delobel, Pierre Cytotoxic CX3CR1+ Vδ1 T cells clonally expand in an interplay of CMV, microbiota, and HIV-1 persistence in people on antiretroviral therapy Journal Article In: PLoS Pathog, vol. 21, no. 9, pp. e1013489, 2025, ISSN: 1553-7374. @article{pmid40920867b,
title = {Cytotoxic CX3CR1+ Vδ1 T cells clonally expand in an interplay of CMV, microbiota, and HIV-1 persistence in people on antiretroviral therapy},
author = {Nived Collercandy and Camille Vellas and Manon Nayrac and Mary Requena and Thomas Richarme and Anne-Laure Iscache and Justine Latour and Karl Barange and Laurent Alric and Guillaume Martin-Blondel and Matteo Serino and Jacques Izopet and Pierre Delobel},
doi = {10.1371/journal.ppat.1013489},
issn = {1553-7374},
year = {2025},
date = {2025-09-01},
urldate = {2025-09-01},
journal = {PLoS Pathog},
volume = {21},
number = {9},
pages = {e1013489},
abstract = {Vδ1 γδ T cells are key players in innate and adaptive immunity, particularly at mucosal interfaces such as the gut. An increase in circulating Vδ1 cells has long been observed in people with HIV-1, but remains poorly understood. We performed a comprehensive characterization of Vδ1 T cells in blood and duodenal intra-epithelial lymphocytes, obtained from endoscopic mucosal biopsies of 15 people with HIV-1 on antiretroviral therapy and 15 HIV-seronegative controls, in a substudy of the ANRS EP61 GALT study (NCT02906137). We deciphered the phenotype, functional profile, single-cell transcriptome and repertoire of Vδ1 cells and unraveled their relationships with the possible triggers involved, in particular CMV and microbiota. We also assessed whether Vδ1 T cells may play a role in controlling the HIV-1 reservoir. Vδ1 T cells were mainly terminally differentiated effectors that clonally expanded in the blood with some trafficking with the gut of people with HIV-1. Most expressed CX3CR1 and displayed a highly cytotoxic profile, but low cytokine production, supported by a transcriptomic shift towards enhanced effector lymphocytes. This expansion was associated with CMV status and markers of occult replication, but also with changes in the duodenal and blood-translocated microbiota. Cytotoxic, but not IFN-γ-producing, Vδ1 T cells were negatively associated with cell-associated HIV-1 RNA in both the blood and duodenal compartments. The increase in Vδ1 T cells observed in people with HIV-1 has multiple triggers, particularly CMV and microbiota, and may in turn contribute to the control of the HIV-1 reservoir.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Vδ1 γδ T cells are key players in innate and adaptive immunity, particularly at mucosal interfaces such as the gut. An increase in circulating Vδ1 cells has long been observed in people with HIV-1, but remains poorly understood. We performed a comprehensive characterization of Vδ1 T cells in blood and duodenal intra-epithelial lymphocytes, obtained from endoscopic mucosal biopsies of 15 people with HIV-1 on antiretroviral therapy and 15 HIV-seronegative controls, in a substudy of the ANRS EP61 GALT study (NCT02906137). We deciphered the phenotype, functional profile, single-cell transcriptome and repertoire of Vδ1 cells and unraveled their relationships with the possible triggers involved, in particular CMV and microbiota. We also assessed whether Vδ1 T cells may play a role in controlling the HIV-1 reservoir. Vδ1 T cells were mainly terminally differentiated effectors that clonally expanded in the blood with some trafficking with the gut of people with HIV-1. Most expressed CX3CR1 and displayed a highly cytotoxic profile, but low cytokine production, supported by a transcriptomic shift towards enhanced effector lymphocytes. This expansion was associated with CMV status and markers of occult replication, but also with changes in the duodenal and blood-translocated microbiota. Cytotoxic, but not IFN-γ-producing, Vδ1 T cells were negatively associated with cell-associated HIV-1 RNA in both the blood and duodenal compartments. The increase in Vδ1 T cells observed in people with HIV-1 has multiple triggers, particularly CMV and microbiota, and may in turn contribute to the control of the HIV-1 reservoir. |
Collercandy, Nived; Vellas, Camille; Nayrac, Manon; Requena, Mary; Richarme, Thomas; Iscache, Anne-Laure; Latour, Justine; Barange, Karl; Alric, Laurent; Martin-Blondel, Guillaume; Serino, Matteo; Izopet, Jacques; Delobel, Pierre Cytotoxic CX3CR1+ Vδ1 T cells clonally expand in an interplay of CMV, microbiota, and HIV-1 persistence in people on antiretroviral therapy Journal Article In: PLoS Pathog, vol. 21, no. 9, pp. e1013489, 2025, ISSN: 1553-7374. @article{pmid40920867,
title = {Cytotoxic CX3CR1+ Vδ1 T cells clonally expand in an interplay of CMV, microbiota, and HIV-1 persistence in people on antiretroviral therapy},
author = {Nived Collercandy and Camille Vellas and Manon Nayrac and Mary Requena and Thomas Richarme and Anne-Laure Iscache and Justine Latour and Karl Barange and Laurent Alric and Guillaume Martin-Blondel and Matteo Serino and Jacques Izopet and Pierre Delobel},
doi = {10.1371/journal.ppat.1013489},
issn = {1553-7374},
year = {2025},
date = {2025-09-01},
urldate = {2025-09-01},
journal = {PLoS Pathog},
volume = {21},
number = {9},
pages = {e1013489},
abstract = {Vδ1 γδ T cells are key players in innate and adaptive immunity, particularly at mucosal interfaces such as the gut. An increase in circulating Vδ1 cells has long been observed in people with HIV-1, but remains poorly understood. We performed a comprehensive characterization of Vδ1 T cells in blood and duodenal intra-epithelial lymphocytes, obtained from endoscopic mucosal biopsies of 15 people with HIV-1 on antiretroviral therapy and 15 HIV-seronegative controls, in a substudy of the ANRS EP61 GALT study (NCT02906137). We deciphered the phenotype, functional profile, single-cell transcriptome and repertoire of Vδ1 cells and unraveled their relationships with the possible triggers involved, in particular CMV and microbiota. We also assessed whether Vδ1 T cells may play a role in controlling the HIV-1 reservoir. Vδ1 T cells were mainly terminally differentiated effectors that clonally expanded in the blood with some trafficking with the gut of people with HIV-1. Most expressed CX3CR1 and displayed a highly cytotoxic profile, but low cytokine production, supported by a transcriptomic shift towards enhanced effector lymphocytes. This expansion was associated with CMV status and markers of occult replication, but also with changes in the duodenal and blood-translocated microbiota. Cytotoxic, but not IFN-γ-producing, Vδ1 T cells were negatively associated with cell-associated HIV-1 RNA in both the blood and duodenal compartments. The increase in Vδ1 T cells observed in people with HIV-1 has multiple triggers, particularly CMV and microbiota, and may in turn contribute to the control of the HIV-1 reservoir.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Vδ1 γδ T cells are key players in innate and adaptive immunity, particularly at mucosal interfaces such as the gut. An increase in circulating Vδ1 cells has long been observed in people with HIV-1, but remains poorly understood. We performed a comprehensive characterization of Vδ1 T cells in blood and duodenal intra-epithelial lymphocytes, obtained from endoscopic mucosal biopsies of 15 people with HIV-1 on antiretroviral therapy and 15 HIV-seronegative controls, in a substudy of the ANRS EP61 GALT study (NCT02906137). We deciphered the phenotype, functional profile, single-cell transcriptome and repertoire of Vδ1 cells and unraveled their relationships with the possible triggers involved, in particular CMV and microbiota. We also assessed whether Vδ1 T cells may play a role in controlling the HIV-1 reservoir. Vδ1 T cells were mainly terminally differentiated effectors that clonally expanded in the blood with some trafficking with the gut of people with HIV-1. Most expressed CX3CR1 and displayed a highly cytotoxic profile, but low cytokine production, supported by a transcriptomic shift towards enhanced effector lymphocytes. This expansion was associated with CMV status and markers of occult replication, but also with changes in the duodenal and blood-translocated microbiota. Cytotoxic, but not IFN-γ-producing, Vδ1 T cells were negatively associated with cell-associated HIV-1 RNA in both the blood and duodenal compartments. The increase in Vδ1 T cells observed in people with HIV-1 has multiple triggers, particularly CMV and microbiota, and may in turn contribute to the control of the HIV-1 reservoir. |
Worrall, William P M; Reber, Laurent L Current and future therapeutics targeting mast cells in disease Journal Article In: Pharmacology & Therapeutics, 2025. @article{Worrall2025,
title = {Current and future therapeutics targeting mast cells in disease},
author = {William P M Worrall and Laurent L Reber},
url = {https://pubmed.ncbi.nlm.nih.gov/40451557/},
doi = {10.1016/j.pharmthera.2025.108892},
year = {2025},
date = {2025-09-01},
urldate = {2025-09-01},
journal = {Pharmacology & Therapeutics},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
F, Martinez; C, Cotineau; C, Bories; L, Culié; S, Rodriguez; C, Pérals; S, Lachambre; V, Duplan-Eche; F, Bucciarelli; B, Pignolet; R, Liblau; L, Michel; M, Aloulou; N, Fazilleau Follicular regulatory T cells promote experimental autoimmune encephalomyelitis by supporting B cell egress from germinal centers. Journal Article In: Science Translational Medecine, vol. 17 , no. 813, 2025. @article{,
title = {Follicular regulatory T cells promote experimental autoimmune encephalomyelitis by supporting B cell egress from germinal centers. },
author = {Martinez F and Cotineau C and Bories C and Culié L and Rodriguez S and Pérals C and Lachambre S and Duplan-Eche V and Bucciarelli F and Pignolet B and Liblau R and Michel L and Aloulou M and Fazilleau N},
doi = {10.1126/scitranslmed.ady1268},
year = {2025},
date = {2025-08-27},
urldate = {2025-08-27},
journal = {Science Translational Medecine},
volume = {17 },
number = {813},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Abdullah NS Serhan N, Gheziel N Maternal stress triggers early-life eczema through fetal mast cell programming Journal Article In: Nature, 2025. @article{serhan2025,
title = {Maternal stress triggers early-life eczema through fetal mast cell programming},
author = {Serhan N, Abdullah NS, Gheziel N, Loste A, Ekren R, Labit E, Gonzalez AA, Oliva G, Tarot P, Petitfils C, Payros G, D'Avino P, Voisin A, Tinsley HFG, Gentek R, Brosseau C, Bodinier M, Reber L, Val P, Akdis CA, Mitamura Y, Andiappan AK, Chan JKY, Ginhoux F, François A, Cénac N, Basso L, Gaudenzio N},
doi = {https://doi.org/10.1038/s41586-025-09419-8},
year = {2025},
date = {2025-08-27},
journal = {Nature},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Chavoshzadeh, Zahra; Fallah, Shahrzad; Zeinali, Vahide; Sharafian, Samin; Delavari, Samaneh; Mesdaghi, Mehrnaz; Djidjik, Reda; Belaid, Brahim; Ikinciogullari, Aydan; Haskologlu, Sule; Dogu, Figen; Genel, Ferah; Gulez, Nesrin; Baris, Safa; Ozen, Ahmet; Karakoc-Aydiner, Elif; Kiykim, Ayça; Meric, Zeynep; Kutukculer, Necil; Aygun, Ayse; Aksu, Guzide; Karaca, Neslihan Edeer; Geyik, Mehmet; Keles, Sevgi; Reisli, Ismail; Guner, Sukru Nail; Boukari, Rachida; Hakem, Saliha; Belbouab, Reda; Barbouche, Mohamed-Ridha; Ben-Mustapha, Imen; Mekki, Najla; Ben-Ali, Meriem; Sobh, Ali; Elnagdy, Marwa; Djenouhat, Kamel; Tahiat, Azzeddine; Shendi, Hiba Mohammed; Alkuwaiti, Amna; Nasrullayeva, Gulnara; Alfars, Tariq; Alsukaiti, Nashat; Massaad, Michel; Mehawej, Cybel; Megarbane, Andre; Irani, Carla; Elghazali, Gehad; Al-Tamemi, Salem; Khalifa, Nisreen; Alzyoud, Raed; Gultekin, Sara Sebnem Kilic; Kose, Hulya; Khodaverdy, Hedieh; Shamsian, Bibi Shahin; Eslami, Narges; Momen, Tooba; Sherkat, Roya; Aleyasin, Soheila; Esmaeilzadeh, Hossein; Ahanchian, Hamid; Salami, Fereshte; Fekrvand, Saba; Dupre, Loïc; Ochs, Hans D.; Rezaei, Nima; Al-Herz, Waleed; Abolhassani, Hassan Clinical and molecular findings in actin-related inborn errors of immunity: the middle East and North Africa registry Journal Article In: Front. Genet., vol. 16, 2025, ISSN: 1664-8021. @article{Chavoshzadeh2025,
title = {Clinical and molecular findings in actin-related inborn errors of immunity: the middle East and North Africa registry},
author = {Zahra Chavoshzadeh and Shahrzad Fallah and Vahide Zeinali and Samin Sharafian and Samaneh Delavari and Mehrnaz Mesdaghi and Reda Djidjik and Brahim Belaid and Aydan Ikinciogullari and Sule Haskologlu and Figen Dogu and Ferah Genel and Nesrin Gulez and Safa Baris and Ahmet Ozen and Elif Karakoc-Aydiner and Ayça Kiykim and Zeynep Meric and Necil Kutukculer and Ayse Aygun and Guzide Aksu and Neslihan Edeer Karaca and Mehmet Geyik and Sevgi Keles and Ismail Reisli and Sukru Nail Guner and Rachida Boukari and Saliha Hakem and Reda Belbouab and Mohamed-Ridha Barbouche and Imen Ben-Mustapha and Najla Mekki and Meriem Ben-Ali and Ali Sobh and Marwa Elnagdy and Kamel Djenouhat and Azzeddine Tahiat and Hiba Mohammed Shendi and Amna Alkuwaiti and Gulnara Nasrullayeva and Tariq Alfars and Nashat Alsukaiti and Michel Massaad and Cybel Mehawej and Andre Megarbane and Carla Irani and Gehad Elghazali and Salem Al-Tamemi and Nisreen Khalifa and Raed Alzyoud and Sara Sebnem Kilic Gultekin and Hulya Kose and Hedieh Khodaverdy and Bibi Shahin Shamsian and Narges Eslami and Tooba Momen and Roya Sherkat and Soheila Aleyasin and Hossein Esmaeilzadeh and Hamid Ahanchian and Fereshte Salami and Saba Fekrvand and Loïc Dupre and Hans D. Ochs and Nima Rezaei and Waleed Al-Herz and Hassan Abolhassani},
doi = {10.3389/fgene.2025.1584681},
issn = {1664-8021},
year = {2025},
date = {2025-08-08},
urldate = {2025-08-08},
journal = {Front. Genet.},
volume = {16},
publisher = {Frontiers Media SA},
abstract = {<jats:sec><jats:title>Background</jats:title><jats:p>The majority of monogenic inborn errors of immunity presenting as actinopathies were reported originally from the Middle East and North Africa (MENA) countries indicating a high prevalence of these entities in the region. However, their prognosis is unclear due to rarity and lack of comprehensive treatment outcomes.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We evaluated clinical, immunological, and genetic abnormalities associated with 15 genetic entities of actinopathies. Based on the function of mutant genes in actin-regulatory pathways, patients were classified into CDC42- and RAC2-related subcategories.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 503 individuals (29.5% females) from 17 countries were considered with a median age of 120 months. Although most patients presented initially with allergic phenotypes (37.7%), the most prevalent manifestations throughout the lifespan were infection in respiratory tracts (72.2%). Primary clinical diagnosis was mainly combined immunodeficiencies (48.3%) and the majority of cases were molecularly assigned to the CDC42 pathway (64.8%). The most common genetic defects were reported within the <jats:italic>DOCK8</jats:italic> (n = 209) followed by the <jats:italic>WAS</jats:italic> (n = 94) and the <jats:italic>CARMIL2</jats:italic> (n = 15) genes. Hematopoietic stem cell transplantation (HSCT) was conducted on 24.0% of patients, which significantly improved survival in patients with defects in <jats:italic>WAS, DOCK8</jats:italic> and <jats:italic>DOCK2</jats:italic>. Overall mortality was 23.0%, mainly due to sepsis and malignancy.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Patients with defects in RAC2-associated regulators of actin usually present with late-onset symptoms due to normal immune profiles, but a higher rate of EBV and HPV infections, autoimmune cytopenia, asthma, and lymphoproliferation compared to defects in the CDC42 pathway. The severity of mutations in patients of the CDC42 group helps to estimate the prognosis of the disease and prioritization of HSCT.</jats:p></jats:sec>},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
<jats:sec><jats:title>Background</jats:title><jats:p>The majority of monogenic inborn errors of immunity presenting as actinopathies were reported originally from the Middle East and North Africa (MENA) countries indicating a high prevalence of these entities in the region. However, their prognosis is unclear due to rarity and lack of comprehensive treatment outcomes.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We evaluated clinical, immunological, and genetic abnormalities associated with 15 genetic entities of actinopathies. Based on the function of mutant genes in actin-regulatory pathways, patients were classified into CDC42- and RAC2-related subcategories.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 503 individuals (29.5% females) from 17 countries were considered with a median age of 120 months. Although most patients presented initially with allergic phenotypes (37.7%), the most prevalent manifestations throughout the lifespan were infection in respiratory tracts (72.2%). Primary clinical diagnosis was mainly combined immunodeficiencies (48.3%) and the majority of cases were molecularly assigned to the CDC42 pathway (64.8%). The most common genetic defects were reported within the <jats:italic>DOCK8</jats:italic> (n = 209) followed by the <jats:italic>WAS</jats:italic> (n = 94) and the <jats:italic>CARMIL2</jats:italic> (n = 15) genes. Hematopoietic stem cell transplantation (HSCT) was conducted on 24.0% of patients, which significantly improved survival in patients with defects in <jats:italic>WAS, DOCK8</jats:italic> and <jats:italic>DOCK2</jats:italic>. Overall mortality was 23.0%, mainly due to sepsis and malignancy.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Patients with defects in RAC2-associated regulators of actin usually present with late-onset symptoms due to normal immune profiles, but a higher rate of EBV and HPV infections, autoimmune cytopenia, asthma, and lymphoproliferation compared to defects in the CDC42 pathway. The severity of mutations in patients of the CDC42 group helps to estimate the prognosis of the disease and prioritization of HSCT.</jats:p></jats:sec> |
Zhang, Brian C; Schneider-Hohendorf, Tilman; Elyanow, Rebecca; Pignolet, Beatrice; Falk, Simon; Wünsch, Christian; Deffner, Marie; Yusko, Erik; May, Damon; Mattox, Daniel; Dawin, Eva; Gerdes, Lisa Ann; Bucciarelli, Florence; Revie, Lisa; Antony, Gisela; Jarius, Sven; Seidel, Christiane; Senel, Makbule; Bittner, Stefan; Luessi, Felix; Havla, Joachim; Knop, Matthias; Friese, Manuel A; Rothacher, Susanne; Salmen, Anke; Hayashi, Fumie; Henry, Roland; Caillier, Stacy; Santaniello, Adam; and,; Seipelt, Maria; Heesen, Christoph; Nischwitz, Sandra; Bayas, Antonios; Tumani, Hayrettin; Bergh, Florian Then; Hörste, Gerd Meyer Zu; Kümpfel, Tania; Gross, Catharina C; Wildemann, Brigitte; Kerschensteiner, Martin; Gold, Ralf; Meuth, Sven G; Zipp, Frauke; Cree, Bruce A C; Oksenberg, Jorge; Wilson, Michael R; Hauser, Stephen L; Zamvil, Scott S; Klotz, Luisa; Liblau, Roland; Robins, Harlan; Sabatino, Joseph J; Wiendl, Heinz; Schwab, Nicholas HLA-A∗03:01 as predictive genetic biomarker for glatiramer acetate treatment response in multiple sclerosis: a retrospective cohort analysis Journal Article In: EBioMedicine, vol. 118, pp. 105873, 2025, ISSN: 2352-3964. @article{pmid40749525b,
title = {HLA-A∗03:01 as predictive genetic biomarker for glatiramer acetate treatment response in multiple sclerosis: a retrospective cohort analysis},
author = {Brian C Zhang and Tilman Schneider-Hohendorf and Rebecca Elyanow and Beatrice Pignolet and Simon Falk and Christian Wünsch and Marie Deffner and Erik Yusko and Damon May and Daniel Mattox and Eva Dawin and Lisa Ann Gerdes and Florence Bucciarelli and Lisa Revie and Gisela Antony and Sven Jarius and Christiane Seidel and Makbule Senel and Stefan Bittner and Felix Luessi and Joachim Havla and Matthias Knop and Manuel A Friese and Susanne Rothacher and Anke Salmen and Fumie Hayashi and Roland Henry and Stacy Caillier and Adam Santaniello and and and Maria Seipelt and Christoph Heesen and Sandra Nischwitz and Antonios Bayas and Hayrettin Tumani and Florian Then Bergh and Gerd Meyer Zu Hörste and Tania Kümpfel and Catharina C Gross and Brigitte Wildemann and Martin Kerschensteiner and Ralf Gold and Sven G Meuth and Frauke Zipp and Bruce A C Cree and Jorge Oksenberg and Michael R Wilson and Stephen L Hauser and Scott S Zamvil and Luisa Klotz and Roland Liblau and Harlan Robins and Joseph J Sabatino and Heinz Wiendl and Nicholas Schwab},
doi = {10.1016/j.ebiom.2025.105873},
issn = {2352-3964},
year = {2025},
date = {2025-08-01},
urldate = {2025-08-01},
journal = {EBioMedicine},
volume = {118},
pages = {105873},
abstract = {BACKGROUND: Glatiramer acetate (GA) is a well-tolerated treatment for multiple sclerosis (MS) and comparable in its efficacy to high-dose interferon beta (IFN). As a lack of validated treatment response biomarkers for MS hampers progress in personalised treatment, the study goal was to search for biomarkers of a successful treatment response utilising the known observation of T-cell expansions after GA treatment.nnMETHODS: T-cell receptor beta chain (TRB) sequencing was performed in 3021 patients with MS: a discovery cohort of 1627 patients with MS, 204 of whom had previously been treated with GA, and then validated in 1394 patients with MS, 424 of whom had previously been treated with GA. Clinical data from 1987 patients with MS treated with GA or IFN and available HLA information from the NationMS, ACP, EPIC, BIONAT, and CombiRx trial cohorts were used for a subsequent analysis.nnFINDINGS: Common GA-associated TRB expansions were exclusively detected in HLA-A∗03:01 or in HLA-DRB1∗15:01 backgrounds, within CD8+ effector- or CD4+ central-memory T cells. Both sets of common sequences clonally expanded after GA treatment in a first validation cohort and predicted GA exposure in two further validation cohorts. To evaluate whether restriction of public TRBs to only two HLA alleles is also associated with GA's clinical efficacy, we analysed five cohorts of patients with MS for a potential benefit of the two HLAs concerning the GA response compared to IFN. We consistently found positive interactions with HLA-A∗03:01. This included a relative reduction in relapse risk compared to IFN in HLA-A∗03:01 carriers of 33% (CombiRx: GA + IFN arm: HR 0.67 [95% CI: 0.47-0.96], p = 0.0269) and 34% (CombiRx: GA arm: HR 0.66 [95% CI: 0.45-0.98], p = 0.0377), and in risk to first relapse of 63% (NationMS: HR 0.37 [95% CI: 0.16-0.88], p = 0.0246), but no positive association with DRB1∗15:01.nnINTERPRETATION: HLA-A∗03:01 carrying patients with MS specifically benefit from GA treatment and GA significantly outperforms IFN in these patients. Therefore, determining HLA-A∗03:01 status before choosing a platform treatment for MS, would allow for a personalised treatment decision between GA and IFN.nnFUNDING: German Research Foundation, National Institutes of Health, National Multiple Sclerosis Society, Valhalla Foundation, Westridge Foundation, Mayer Foundation, German Federal Ministry of Education and Research.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Glatiramer acetate (GA) is a well-tolerated treatment for multiple sclerosis (MS) and comparable in its efficacy to high-dose interferon beta (IFN). As a lack of validated treatment response biomarkers for MS hampers progress in personalised treatment, the study goal was to search for biomarkers of a successful treatment response utilising the known observation of T-cell expansions after GA treatment.nnMETHODS: T-cell receptor beta chain (TRB) sequencing was performed in 3021 patients with MS: a discovery cohort of 1627 patients with MS, 204 of whom had previously been treated with GA, and then validated in 1394 patients with MS, 424 of whom had previously been treated with GA. Clinical data from 1987 patients with MS treated with GA or IFN and available HLA information from the NationMS, ACP, EPIC, BIONAT, and CombiRx trial cohorts were used for a subsequent analysis.nnFINDINGS: Common GA-associated TRB expansions were exclusively detected in HLA-A∗03:01 or in HLA-DRB1∗15:01 backgrounds, within CD8+ effector- or CD4+ central-memory T cells. Both sets of common sequences clonally expanded after GA treatment in a first validation cohort and predicted GA exposure in two further validation cohorts. To evaluate whether restriction of public TRBs to only two HLA alleles is also associated with GA's clinical efficacy, we analysed five cohorts of patients with MS for a potential benefit of the two HLAs concerning the GA response compared to IFN. We consistently found positive interactions with HLA-A∗03:01. This included a relative reduction in relapse risk compared to IFN in HLA-A∗03:01 carriers of 33% (CombiRx: GA + IFN arm: HR 0.67 [95% CI: 0.47-0.96], p = 0.0269) and 34% (CombiRx: GA arm: HR 0.66 [95% CI: 0.45-0.98], p = 0.0377), and in risk to first relapse of 63% (NationMS: HR 0.37 [95% CI: 0.16-0.88], p = 0.0246), but no positive association with DRB1∗15:01.nnINTERPRETATION: HLA-A∗03:01 carrying patients with MS specifically benefit from GA treatment and GA significantly outperforms IFN in these patients. Therefore, determining HLA-A∗03:01 status before choosing a platform treatment for MS, would allow for a personalised treatment decision between GA and IFN.nnFUNDING: German Research Foundation, National Institutes of Health, National Multiple Sclerosis Society, Valhalla Foundation, Westridge Foundation, Mayer Foundation, German Federal Ministry of Education and Research. |
Hernández-Martín, Ángela; Paller, Amy S; Sprecher, Eli; Akiyama, Masashi; Tournier, Céline Granier; Aldwin-Easton, Mandy; Bodemer, Christine; Choate, Keith; Fischer, Judith; Gostynski, Antoni; Hovnanian, Alain; Ishida-Yamamoto, Akemi; O'Toole, Edel A; Schmuth, Matthias; Schwartz, Janice; Tadini, Gianluca; Teng, Joyce; Mazereeuw-Hautier, Juliette A proposal for a new pathogenesis-guided classification for inherited epidermal differentiation disorders Journal Article In: Br J Dermatol, vol. 193, no. 3, pp. 544–548, 2025, ISSN: 1365-2133. @article{pmid40155206,
title = {A proposal for a new pathogenesis-guided classification for inherited epidermal differentiation disorders},
author = {Ángela Hernández-Martín and Amy S Paller and Eli Sprecher and Masashi Akiyama and Céline Granier Tournier and Mandy Aldwin-Easton and Christine Bodemer and Keith Choate and Judith Fischer and Antoni Gostynski and Alain Hovnanian and Akemi Ishida-Yamamoto and Edel A O'Toole and Matthias Schmuth and Janice Schwartz and Gianluca Tadini and Joyce Teng and Juliette Mazereeuw-Hautier},
doi = {10.1093/bjd/ljaf065},
issn = {1365-2133},
year = {2025},
date = {2025-08-01},
urldate = {2025-08-01},
journal = {Br J Dermatol},
volume = {193},
number = {3},
pages = {544--548},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Zhang, Brian C; Schneider-Hohendorf, Tilman; Elyanow, Rebecca; Pignolet, Beatrice; Falk, Simon; Wünsch, Christian; Deffner, Marie; Yusko, Erik; May, Damon; Mattox, Daniel; Dawin, Eva; Gerdes, Lisa Ann; Bucciarelli, Florence; Revie, Lisa; Antony, Gisela; Jarius, Sven; Seidel, Christiane; Senel, Makbule; Bittner, Stefan; Luessi, Felix; Havla, Joachim; Knop, Matthias; Friese, Manuel A; Rothacher, Susanne; Salmen, Anke; Hayashi, Fumie; Henry, Roland; Caillier, Stacy; Santaniello, Adam; and,; Seipelt, Maria; Heesen, Christoph; Nischwitz, Sandra; Bayas, Antonios; Tumani, Hayrettin; Bergh, Florian Then; Hörste, Gerd Meyer Zu; Kümpfel, Tania; Gross, Catharina C; Wildemann, Brigitte; Kerschensteiner, Martin; Gold, Ralf; Meuth, Sven G; Zipp, Frauke; Cree, Bruce A C; Oksenberg, Jorge; Wilson, Michael R; Hauser, Stephen L; Zamvil, Scott S; Klotz, Luisa; Liblau, Roland; Robins, Harlan; Sabatino, Joseph J; Wiendl, Heinz; Schwab, Nicholas HLA-A∗03:01 as predictive genetic biomarker for glatiramer acetate treatment response in multiple sclerosis: a retrospective cohort analysis Journal Article In: EBioMedicine, vol. 118, pp. 105873, 2025, ISSN: 2352-3964. @article{pmid40749525,
title = {HLA-A∗03:01 as predictive genetic biomarker for glatiramer acetate treatment response in multiple sclerosis: a retrospective cohort analysis},
author = {Brian C Zhang and Tilman Schneider-Hohendorf and Rebecca Elyanow and Beatrice Pignolet and Simon Falk and Christian Wünsch and Marie Deffner and Erik Yusko and Damon May and Daniel Mattox and Eva Dawin and Lisa Ann Gerdes and Florence Bucciarelli and Lisa Revie and Gisela Antony and Sven Jarius and Christiane Seidel and Makbule Senel and Stefan Bittner and Felix Luessi and Joachim Havla and Matthias Knop and Manuel A Friese and Susanne Rothacher and Anke Salmen and Fumie Hayashi and Roland Henry and Stacy Caillier and Adam Santaniello and and and Maria Seipelt and Christoph Heesen and Sandra Nischwitz and Antonios Bayas and Hayrettin Tumani and Florian Then Bergh and Gerd Meyer Zu Hörste and Tania Kümpfel and Catharina C Gross and Brigitte Wildemann and Martin Kerschensteiner and Ralf Gold and Sven G Meuth and Frauke Zipp and Bruce A C Cree and Jorge Oksenberg and Michael R Wilson and Stephen L Hauser and Scott S Zamvil and Luisa Klotz and Roland Liblau and Harlan Robins and Joseph J Sabatino and Heinz Wiendl and Nicholas Schwab},
doi = {10.1016/j.ebiom.2025.105873},
issn = {2352-3964},
year = {2025},
date = {2025-08-01},
urldate = {2025-08-01},
journal = {EBioMedicine},
volume = {118},
pages = {105873},
abstract = {BACKGROUND: Glatiramer acetate (GA) is a well-tolerated treatment for multiple sclerosis (MS) and comparable in its efficacy to high-dose interferon beta (IFN). As a lack of validated treatment response biomarkers for MS hampers progress in personalised treatment, the study goal was to search for biomarkers of a successful treatment response utilising the known observation of T-cell expansions after GA treatment.nnMETHODS: T-cell receptor beta chain (TRB) sequencing was performed in 3021 patients with MS: a discovery cohort of 1627 patients with MS, 204 of whom had previously been treated with GA, and then validated in 1394 patients with MS, 424 of whom had previously been treated with GA. Clinical data from 1987 patients with MS treated with GA or IFN and available HLA information from the NationMS, ACP, EPIC, BIONAT, and CombiRx trial cohorts were used for a subsequent analysis.nnFINDINGS: Common GA-associated TRB expansions were exclusively detected in HLA-A∗03:01 or in HLA-DRB1∗15:01 backgrounds, within CD8+ effector- or CD4+ central-memory T cells. Both sets of common sequences clonally expanded after GA treatment in a first validation cohort and predicted GA exposure in two further validation cohorts. To evaluate whether restriction of public TRBs to only two HLA alleles is also associated with GA's clinical efficacy, we analysed five cohorts of patients with MS for a potential benefit of the two HLAs concerning the GA response compared to IFN. We consistently found positive interactions with HLA-A∗03:01. This included a relative reduction in relapse risk compared to IFN in HLA-A∗03:01 carriers of 33% (CombiRx: GA + IFN arm: HR 0.67 [95% CI: 0.47-0.96], p = 0.0269) and 34% (CombiRx: GA arm: HR 0.66 [95% CI: 0.45-0.98], p = 0.0377), and in risk to first relapse of 63% (NationMS: HR 0.37 [95% CI: 0.16-0.88], p = 0.0246), but no positive association with DRB1∗15:01.nnINTERPRETATION: HLA-A∗03:01 carrying patients with MS specifically benefit from GA treatment and GA significantly outperforms IFN in these patients. Therefore, determining HLA-A∗03:01 status before choosing a platform treatment for MS, would allow for a personalised treatment decision between GA and IFN.nnFUNDING: German Research Foundation, National Institutes of Health, National Multiple Sclerosis Society, Valhalla Foundation, Westridge Foundation, Mayer Foundation, German Federal Ministry of Education and Research.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Glatiramer acetate (GA) is a well-tolerated treatment for multiple sclerosis (MS) and comparable in its efficacy to high-dose interferon beta (IFN). As a lack of validated treatment response biomarkers for MS hampers progress in personalised treatment, the study goal was to search for biomarkers of a successful treatment response utilising the known observation of T-cell expansions after GA treatment.nnMETHODS: T-cell receptor beta chain (TRB) sequencing was performed in 3021 patients with MS: a discovery cohort of 1627 patients with MS, 204 of whom had previously been treated with GA, and then validated in 1394 patients with MS, 424 of whom had previously been treated with GA. Clinical data from 1987 patients with MS treated with GA or IFN and available HLA information from the NationMS, ACP, EPIC, BIONAT, and CombiRx trial cohorts were used for a subsequent analysis.nnFINDINGS: Common GA-associated TRB expansions were exclusively detected in HLA-A∗03:01 or in HLA-DRB1∗15:01 backgrounds, within CD8+ effector- or CD4+ central-memory T cells. Both sets of common sequences clonally expanded after GA treatment in a first validation cohort and predicted GA exposure in two further validation cohorts. To evaluate whether restriction of public TRBs to only two HLA alleles is also associated with GA's clinical efficacy, we analysed five cohorts of patients with MS for a potential benefit of the two HLAs concerning the GA response compared to IFN. We consistently found positive interactions with HLA-A∗03:01. This included a relative reduction in relapse risk compared to IFN in HLA-A∗03:01 carriers of 33% (CombiRx: GA + IFN arm: HR 0.67 [95% CI: 0.47-0.96], p = 0.0269) and 34% (CombiRx: GA arm: HR 0.66 [95% CI: 0.45-0.98], p = 0.0377), and in risk to first relapse of 63% (NationMS: HR 0.37 [95% CI: 0.16-0.88], p = 0.0246), but no positive association with DRB1∗15:01.nnINTERPRETATION: HLA-A∗03:01 carrying patients with MS specifically benefit from GA treatment and GA significantly outperforms IFN in these patients. Therefore, determining HLA-A∗03:01 status before choosing a platform treatment for MS, would allow for a personalised treatment decision between GA and IFN.nnFUNDING: German Research Foundation, National Institutes of Health, National Multiple Sclerosis Society, Valhalla Foundation, Westridge Foundation, Mayer Foundation, German Federal Ministry of Education and Research. |
Belloy, Marcy; Schmitt, Benjamin A M; Marty, Florent H; Paut, Charlotte; Bassot, Emilie; Aïda, Amel; Alis, Marine; Zahm, Margot; Chaubet, Adeline; Garnier, Hugo; Flores-Aguilar, Thelma; Roitg, Elisa; Gutierrez-Loli, Renzo; Allart, Sophie; Ecalard, Romain; Boursereau, Raphaël; Ligat, Gaëtan; Gonzalez-Dunia, Daniel; Blanchard, Nicolas; Suberbielle, Elsa Toxoplasma gondii infection and chronic IL-1 elevation drive hippocampal DNA double-strand break signaling, leading to cognitive deficits Journal Article In: Nat Neurosci, 2025, ISSN: 1546-1726. @article{pmid40841478,
title = {Toxoplasma gondii infection and chronic IL-1 elevation drive hippocampal DNA double-strand break signaling, leading to cognitive deficits},
author = {Marcy Belloy and Benjamin A M Schmitt and Florent H Marty and Charlotte Paut and Emilie Bassot and Amel Aïda and Marine Alis and Margot Zahm and Adeline Chaubet and Hugo Garnier and Thelma Flores-Aguilar and Elisa Roitg and Renzo Gutierrez-Loli and Sophie Allart and Romain Ecalard and Raphaël Boursereau and Gaëtan Ligat and Daniel Gonzalez-Dunia and Nicolas Blanchard and Elsa Suberbielle},
doi = {10.1038/s41593-025-02041-x},
issn = {1546-1726},
year = {2025},
date = {2025-08-01},
urldate = {2025-08-01},
journal = {Nat Neurosci},
abstract = {Chronic inflammation, resulting from infections, is characterized by increased levels of cytokines including interleukin-1 (IL-1), but little is known about how IL-1 contributes to cognitive impairment, potentially via epigenetic processes. Here we demonstrate that mice chronically infected with the parasite Toxoplasma gondii exhibit impaired spatial memory, which is dependent on neuronal IL-1 signaling and mimicked by chronic exposure to IL-1β. Both T. gondii infection and chronic IL-1β drive H2A.X-dependent DNA double-strand break signaling in hippocampal neurons and invalidating neuronal H2A.X-dependent signaling blocks memory impairments caused by either exposure. Our results highlight the instrumental role of cytokine-induced double-strand-break-dependent signaling in spatial memory defects, which may be relevant to multiple brain diseases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Chronic inflammation, resulting from infections, is characterized by increased levels of cytokines including interleukin-1 (IL-1), but little is known about how IL-1 contributes to cognitive impairment, potentially via epigenetic processes. Here we demonstrate that mice chronically infected with the parasite Toxoplasma gondii exhibit impaired spatial memory, which is dependent on neuronal IL-1 signaling and mimicked by chronic exposure to IL-1β. Both T. gondii infection and chronic IL-1β drive H2A.X-dependent DNA double-strand break signaling in hippocampal neurons and invalidating neuronal H2A.X-dependent signaling blocks memory impairments caused by either exposure. Our results highlight the instrumental role of cytokine-induced double-strand-break-dependent signaling in spatial memory defects, which may be relevant to multiple brain diseases. |
Mafi, Sarah; Poyet, Jean-Luc; Alain, Sophie; Ligat, Gaëtan; Hantz, Sébastien First evidence of efficacy of peptides targeting the pUL56-pUL89 interaction domain of the human cytomegalovirus terminase complex Journal Article In: Antiviral Res, pp. 106259, 2025, ISSN: 1872-9096. @article{pmid40816464,
title = {First evidence of efficacy of peptides targeting the pUL56-pUL89 interaction domain of the human cytomegalovirus terminase complex},
author = {Sarah Mafi and Jean-Luc Poyet and Sophie Alain and Gaëtan Ligat and Sébastien Hantz},
doi = {10.1016/j.antiviral.2025.106259},
issn = {1872-9096},
year = {2025},
date = {2025-08-01},
urldate = {2025-08-01},
journal = {Antiviral Res},
pages = {106259},
abstract = {Human cytomegalovirus (HCMV) is a major cause of morbidity in immunocompromised patients and the leading viral cause of congenital infection. The toxicity and emergence of resistance associated with current antivirals underscore the need for alternative therapeutic strategies. The viral terminase complex (pUL56-pUL89-pUL51), essential for genome cleavage and packaging and without homologs in mammalian cells, represents a promising antiviral target. This study evaluated the antiviral potential of peptides targeting the pUL56-pUL89 interaction domain. Peptides derived from the minimal interaction domain between pUL56 and pUL89 (WF10: WMVVKYMGFF) or an extended sequence (PD17: PSEWMVVKYMGFFNFSD) were synthesized to interfere with this interaction. To optimize intracellular delivery, peptides were conjugated to a cell-penetrating peptide (CPP) derived from either the HIV-1 transactivator of transcription (TAT) or the Antennapedia homeodomain of Drosophila melanogaster (penetratin; PT). Peptide candidates- PT-WF10, TAT-WF10, and PT-PD17- were evaluated in cellular models for cytotoxicity, hemolysis, antiviral activity, and intracellular distribution. TAT-WF10 and PT-PD17 significantly reduced the cytopathic foci in HCMV-infected cells, with IC values of 58 μM and 39 μM, respectively. PT-WF10 lacked antiviral activity, induced significant cytotoxicity and hemolysis, and was mainly localized in the cytoplasm, with only minimal nuclear signal. TAT-WF10 showed cytoplasmic and nuclear distribution, no hemolysis, but induced long-term cytotoxicity from 40 μM. PT-PD17 exhibited cytoplasmic and nuclear distribution, with no significant cytotoxicity or hemolysis up to 80 μM. This study provides the first proof of concept that a peptide targeting the pUL56-pUL89 interaction domain can inhibit HCMV replication. PT-PD17 demonstrated antiviral activity, intracellular distribution, and a favorable safety profile.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Human cytomegalovirus (HCMV) is a major cause of morbidity in immunocompromised patients and the leading viral cause of congenital infection. The toxicity and emergence of resistance associated with current antivirals underscore the need for alternative therapeutic strategies. The viral terminase complex (pUL56-pUL89-pUL51), essential for genome cleavage and packaging and without homologs in mammalian cells, represents a promising antiviral target. This study evaluated the antiviral potential of peptides targeting the pUL56-pUL89 interaction domain. Peptides derived from the minimal interaction domain between pUL56 and pUL89 (WF10: WMVVKYMGFF) or an extended sequence (PD17: PSEWMVVKYMGFFNFSD) were synthesized to interfere with this interaction. To optimize intracellular delivery, peptides were conjugated to a cell-penetrating peptide (CPP) derived from either the HIV-1 transactivator of transcription (TAT) or the Antennapedia homeodomain of Drosophila melanogaster (penetratin; PT). Peptide candidates- PT-WF10, TAT-WF10, and PT-PD17- were evaluated in cellular models for cytotoxicity, hemolysis, antiviral activity, and intracellular distribution. TAT-WF10 and PT-PD17 significantly reduced the cytopathic foci in HCMV-infected cells, with IC values of 58 μM and 39 μM, respectively. PT-WF10 lacked antiviral activity, induced significant cytotoxicity and hemolysis, and was mainly localized in the cytoplasm, with only minimal nuclear signal. TAT-WF10 showed cytoplasmic and nuclear distribution, no hemolysis, but induced long-term cytotoxicity from 40 μM. PT-PD17 exhibited cytoplasmic and nuclear distribution, with no significant cytotoxicity or hemolysis up to 80 μM. This study provides the first proof of concept that a peptide targeting the pUL56-pUL89 interaction domain can inhibit HCMV replication. PT-PD17 demonstrated antiviral activity, intracellular distribution, and a favorable safety profile. |
Kamphuis, Jasper B J; Loste, Alexia; Worrall, William P M; Serhan, Nadine; Villeneuve, Thomas; Apoil, Pol André; Trouche-Estival, Benjamin; group, IHU HealthAge INSPIRE/Open Science; Guilleminault, Laurent; Gaudenzio, Nicolas; Reber, Laurent L Aging Increases the Severity of Anaphylaxis Through Changes in Mast Cell Numbers and Histamine Sensitivity Journal Article In: Allergy, 2025. @article{nokey,
title = {Aging Increases the Severity of Anaphylaxis Through Changes in Mast Cell Numbers and Histamine Sensitivity},
author = {Jasper B J Kamphuis and Alexia Loste and William P M Worrall and Nadine Serhan and Thomas Villeneuve and Pol André Apoil and Benjamin Trouche-Estival and IHU HealthAge INSPIRE/Open Science group and Laurent Guilleminault and Nicolas Gaudenzio and Laurent L Reber
},
url = {https://pubmed.ncbi.nlm.nih.gov/40654257/},
doi = {10.1111/all.16650},
year = {2025},
date = {2025-07-14},
urldate = {2025-07-14},
journal = {Allergy},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Ansaldo, Eduard; Yong, Daniel; Carrillo, Nathan; McFadden, Taryn; Abid, Mahnoor; Corral, Dan; Rivera, Claudia; Farley, Taylor; Bouladoux, Nicolas; Gribonika, Inta; Belkaid, Yasmine T-bet expressing Tr1 cells driven by dietary signals dominate the small intestinal immune landscape Journal Article In: bioRxiv, 2025, ISSN: 2692-8205. @article{pmid40747421b,
title = {T-bet expressing Tr1 cells driven by dietary signals dominate the small intestinal immune landscape},
author = {Eduard Ansaldo and Daniel Yong and Nathan Carrillo and Taryn McFadden and Mahnoor Abid and Dan Corral and Claudia Rivera and Taylor Farley and Nicolas Bouladoux and Inta Gribonika and Yasmine Belkaid},
doi = {10.1101/2025.06.30.662190},
issn = {2692-8205},
year = {2025},
date = {2025-07-01},
journal = {bioRxiv},
abstract = {Intestinal immunity defends against enteric pathogens, mediates symbiotic relationships with the resident microbiota, and provides tolerance to food antigens, safeguarding critical nutrient absorption and barrier functions of this mucosal tissue. Despite the abundance of tissue resident activated T cells, their contributions to these various roles remains poorly understood. Here, we identify a dominant population of IL-10 producing, T-bet expressing CD4+ Tr1 T cells, residing in the small intestinal lamina propria at homeostasis. Remarkably, these intestinal Tr1 cells emerge at the time of weaning and accumulate independently of the microbiota displaying similar abundance, function and TCR repertoire under germ-free conditions. Instead, the small intestinal T-bet+ Tr1 program is driven and shaped by dietary antigens, and accumulates in a cDC1-IL-27 dependent manner. Upon activation, these cells robustly express IL-10 and multiple inhibitory receptors, establishing a distinct suppressive profile. Altogether, this work uncovers a previously unappreciated dominant player in homeostatic small intestinal immunity with the potential to play critical suppressive roles in this tissue, raising important implications for the understanding of immune regulation in the intestine.nnSIGNIFICANCE STATEMENT: Establishing immunological tolerance to self and environmental antigens is critical to preserve tissue homeostasis and function. In the intestine, both dietary and microbiota derived antigens are routinely encountered by the immune system, which deploys a variety of mechanisms to maintain tolerance to these innocuous antigens. Understanding how immunological tolerance is established is critical, a when this process goes awry it can lead to severe inflammatory and autoimmune diseases such as food allergy and inflammatory bowel disease. However, how tolerance is established in the intestine is still poorly understood. In this study we describe a novel dominant T cell population in the small intestine shaped by dietary components with the potential to play important roles in immune tolerance at this site. back # IntroductionBarrier surfaces such as the gut and skin represent the first line of defense against the environment. These organs must strike a delicate balance between providing protection against environmental and infectious agents, maintaining tissue function, and establishing a homeostatic symbiotic relationship with resident microbes collectively known as the microbiota (1). The immune system plays a critical role in establishing these dynamic and carefully regulated relationships, as evidenced by the large number of immune cells present at these sites. Of particular note, activated T cells are very abundant at barrier tissues, where they orchestrate immune effector functions geared towards these varied tasks (1, 2). In the small intestine, the intraepithelial compartment harbors innate like natural CD8aa⁺ IELs, many of which are self reactive; as well as CD4⁺CD8aa⁺ and CD8ab⁺ IELs responding to dietary and microbial antigens (3). The underlying lamina propria (SILP) harbors predominantly CD4⁺ T cells, which participate in responses to commensal-derived and dietary antigens (2, 4). Despite the abundance of small intestinal CD4 T cells, only a handful of cognate immune interactions focusing on Type 17 and T regulatory helper subsets have been described. Thus, whether immune responses in this tissue are truly limited to a small number of antigenic triggers and effector functions remains to be fully elucidated. The small number of gut homeostatic CD4 T cell responses described thus far have been shown to primarily respond to specific commensal bacteria or dietary antigens (1, 2, 5-8): Among other examples, SFB induces cognate Th17 cells in the small intestine (9, 10), a consortium human commensal bacteria induces CD8b⁺ cells in the colon (11), and indices T and other effector cells in the Peyer's patches and lamina propria, respectively (12). Furthermore most regulatory T cells in the colon are induced in response to commensal or pathobiont species at homeostasis, providing critical regulatory functions (13, 14). Cognate immune responses to SFB help contain this commensal species in the intestine (15), but also have systemic impacts on the susceptibility to autoimmune disease (16, 17). Interestingly, despite presenting a classical Th17 effector profile, a subset of SFB-induced Th17 cells possess IL-10 secretion capabilities and suppress cognate immune responses without the expression of Foxp3 (18), suggesting immunoregulatory functions reminiscent of Tr1 cells. Whether these competing capabilities are unique to SFB-specific immune responses or a general hallmark of small intestinal immunity remains unknown. The description of SFB-specific Tr1-like cells in the small intestine was surprising, as this CD4⁺ T cell subset, characterized by abundant IL-10 secretion in the absence of expression, has only been described in the context of chronic antigen stimulation, such as chronic infection or cancer (19). The Tr1 cell program is controlled by a variety of transcription factors and upstream signaling pathways, including IL-27 signaling, MAF and AHR (20). AHR-ligands are abundant in the intestine, and MAF is a hallmark of other regulatory commensal-specific responses (21, 14). Furthermore, IL-27, which can induce both proinflammatory and immunoregulatory functions, is abundant in the small intestine (22, 23). This raises the possibility that the Tr1 program is a more general feature of small intestinal immunity, not uniquely restricted to SFB-specific responses. In this study we explore the breadth of CD4⁺ T cell responses in the small intestine, and uncover a previously uncharacterized CD4⁺T-bet⁺ T cell immune response that is dominant in this tissue. Unexpectedly, these SILP CD4⁺T-bet⁺ T cells are independent of the microbiota, maintaining a similar functional profile and shared antigen specificities in germ-free conditions. Instead, we reveal that dietary components drive the accumulation, function, and clonal selection of this T cell population. Finally, we show that, contrary to classical Th1 cells, SILP CD4⁺T-bet⁺ T cells adopt a Tr1 immunoregulatory functional program during activation, suggesting that this is a general feature of CD4⁺ T cell immunity in the small intestine wired towards immune regulation and tissue homeostasis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Intestinal immunity defends against enteric pathogens, mediates symbiotic relationships with the resident microbiota, and provides tolerance to food antigens, safeguarding critical nutrient absorption and barrier functions of this mucosal tissue. Despite the abundance of tissue resident activated T cells, their contributions to these various roles remains poorly understood. Here, we identify a dominant population of IL-10 producing, T-bet expressing CD4+ Tr1 T cells, residing in the small intestinal lamina propria at homeostasis. Remarkably, these intestinal Tr1 cells emerge at the time of weaning and accumulate independently of the microbiota displaying similar abundance, function and TCR repertoire under germ-free conditions. Instead, the small intestinal T-bet+ Tr1 program is driven and shaped by dietary antigens, and accumulates in a cDC1-IL-27 dependent manner. Upon activation, these cells robustly express IL-10 and multiple inhibitory receptors, establishing a distinct suppressive profile. Altogether, this work uncovers a previously unappreciated dominant player in homeostatic small intestinal immunity with the potential to play critical suppressive roles in this tissue, raising important implications for the understanding of immune regulation in the intestine.nnSIGNIFICANCE STATEMENT: Establishing immunological tolerance to self and environmental antigens is critical to preserve tissue homeostasis and function. In the intestine, both dietary and microbiota derived antigens are routinely encountered by the immune system, which deploys a variety of mechanisms to maintain tolerance to these innocuous antigens. Understanding how immunological tolerance is established is critical, a when this process goes awry it can lead to severe inflammatory and autoimmune diseases such as food allergy and inflammatory bowel disease. However, how tolerance is established in the intestine is still poorly understood. In this study we describe a novel dominant T cell population in the small intestine shaped by dietary components with the potential to play important roles in immune tolerance at this site. back # IntroductionBarrier surfaces such as the gut and skin represent the first line of defense against the environment. These organs must strike a delicate balance between providing protection against environmental and infectious agents, maintaining tissue function, and establishing a homeostatic symbiotic relationship with resident microbes collectively known as the microbiota (1). The immune system plays a critical role in establishing these dynamic and carefully regulated relationships, as evidenced by the large number of immune cells present at these sites. Of particular note, activated T cells are very abundant at barrier tissues, where they orchestrate immune effector functions geared towards these varied tasks (1, 2). In the small intestine, the intraepithelial compartment harbors innate like natural CD8aa⁺ IELs, many of which are self reactive; as well as CD4⁺CD8aa⁺ and CD8ab⁺ IELs responding to dietary and microbial antigens (3). The underlying lamina propria (SILP) harbors predominantly CD4⁺ T cells, which participate in responses to commensal-derived and dietary antigens (2, 4). Despite the abundance of small intestinal CD4 T cells, only a handful of cognate immune interactions focusing on Type 17 and T regulatory helper subsets have been described. Thus, whether immune responses in this tissue are truly limited to a small number of antigenic triggers and effector functions remains to be fully elucidated. The small number of gut homeostatic CD4 T cell responses described thus far have been shown to primarily respond to specific commensal bacteria or dietary antigens (1, 2, 5-8): Among other examples, SFB induces cognate Th17 cells in the small intestine (9, 10), a consortium human commensal bacteria induces CD8b⁺ cells in the colon (11), and indices T and other effector cells in the Peyer's patches and lamina propria, respectively (12). Furthermore most regulatory T cells in the colon are induced in response to commensal or pathobiont species at homeostasis, providing critical regulatory functions (13, 14). Cognate immune responses to SFB help contain this commensal species in the intestine (15), but also have systemic impacts on the susceptibility to autoimmune disease (16, 17). Interestingly, despite presenting a classical Th17 effector profile, a subset of SFB-induced Th17 cells possess IL-10 secretion capabilities and suppress cognate immune responses without the expression of Foxp3 (18), suggesting immunoregulatory functions reminiscent of Tr1 cells. Whether these competing capabilities are unique to SFB-specific immune responses or a general hallmark of small intestinal immunity remains unknown. The description of SFB-specific Tr1-like cells in the small intestine was surprising, as this CD4⁺ T cell subset, characterized by abundant IL-10 secretion in the absence of expression, has only been described in the context of chronic antigen stimulation, such as chronic infection or cancer (19). The Tr1 cell program is controlled by a variety of transcription factors and upstream signaling pathways, including IL-27 signaling, MAF and AHR (20). AHR-ligands are abundant in the intestine, and MAF is a hallmark of other regulatory commensal-specific responses (21, 14). Furthermore, IL-27, which can induce both proinflammatory and immunoregulatory functions, is abundant in the small intestine (22, 23). This raises the possibility that the Tr1 program is a more general feature of small intestinal immunity, not uniquely restricted to SFB-specific responses. In this study we explore the breadth of CD4⁺ T cell responses in the small intestine, and uncover a previously uncharacterized CD4⁺T-bet⁺ T cell immune response that is dominant in this tissue. Unexpectedly, these SILP CD4⁺T-bet⁺ T cells are independent of the microbiota, maintaining a similar functional profile and shared antigen specificities in germ-free conditions. Instead, we reveal that dietary components drive the accumulation, function, and clonal selection of this T cell population. Finally, we show that, contrary to classical Th1 cells, SILP CD4⁺T-bet⁺ T cells adopt a Tr1 immunoregulatory functional program during activation, suggesting that this is a general feature of CD4⁺ T cell immunity in the small intestine wired towards immune regulation and tissue homeostasis. |
Ansaldo, Eduard; Yong, Daniel; Carrillo, Nathan; McFadden, Taryn; Abid, Mahnoor; Corral, Dan; Rivera, Claudia; Farley, Taylor; Bouladoux, Nicolas; Gribonika, Inta; Belkaid, Yasmine T-bet expressing Tr1 cells driven by dietary signals dominate the small intestinal immune landscape Journal Article In: bioRxiv, 2025, ISSN: 2692-8205. @article{pmid40747421,
title = {T-bet expressing Tr1 cells driven by dietary signals dominate the small intestinal immune landscape},
author = {Eduard Ansaldo and Daniel Yong and Nathan Carrillo and Taryn McFadden and Mahnoor Abid and Dan Corral and Claudia Rivera and Taylor Farley and Nicolas Bouladoux and Inta Gribonika and Yasmine Belkaid},
doi = {10.1101/2025.06.30.662190},
issn = {2692-8205},
year = {2025},
date = {2025-07-01},
journal = {bioRxiv},
abstract = {Intestinal immunity defends against enteric pathogens, mediates symbiotic relationships with the resident microbiota, and provides tolerance to food antigens, safeguarding critical nutrient absorption and barrier functions of this mucosal tissue. Despite the abundance of tissue resident activated T cells, their contributions to these various roles remains poorly understood. Here, we identify a dominant population of IL-10 producing, T-bet expressing CD4+ Tr1 T cells, residing in the small intestinal lamina propria at homeostasis. Remarkably, these intestinal Tr1 cells emerge at the time of weaning and accumulate independently of the microbiota displaying similar abundance, function and TCR repertoire under germ-free conditions. Instead, the small intestinal T-bet+ Tr1 program is driven and shaped by dietary antigens, and accumulates in a cDC1-IL-27 dependent manner. Upon activation, these cells robustly express IL-10 and multiple inhibitory receptors, establishing a distinct suppressive profile. Altogether, this work uncovers a previously unappreciated dominant player in homeostatic small intestinal immunity with the potential to play critical suppressive roles in this tissue, raising important implications for the understanding of immune regulation in the intestine.nnSIGNIFICANCE STATEMENT: Establishing immunological tolerance to self and environmental antigens is critical to preserve tissue homeostasis and function. In the intestine, both dietary and microbiota derived antigens are routinely encountered by the immune system, which deploys a variety of mechanisms to maintain tolerance to these innocuous antigens. Understanding how immunological tolerance is established is critical, a when this process goes awry it can lead to severe inflammatory and autoimmune diseases such as food allergy and inflammatory bowel disease. However, how tolerance is established in the intestine is still poorly understood. In this study we describe a novel dominant T cell population in the small intestine shaped by dietary components with the potential to play important roles in immune tolerance at this site. back # IntroductionBarrier surfaces such as the gut and skin represent the first line of defense against the environment. These organs must strike a delicate balance between providing protection against environmental and infectious agents, maintaining tissue function, and establishing a homeostatic symbiotic relationship with resident microbes collectively known as the microbiota (1). The immune system plays a critical role in establishing these dynamic and carefully regulated relationships, as evidenced by the large number of immune cells present at these sites. Of particular note, activated T cells are very abundant at barrier tissues, where they orchestrate immune effector functions geared towards these varied tasks (1, 2). In the small intestine, the intraepithelial compartment harbors innate like natural CD8aa⁺ IELs, many of which are self reactive; as well as CD4⁺CD8aa⁺ and CD8ab⁺ IELs responding to dietary and microbial antigens (3). The underlying lamina propria (SILP) harbors predominantly CD4⁺ T cells, which participate in responses to commensal-derived and dietary antigens (2, 4). Despite the abundance of small intestinal CD4 T cells, only a handful of cognate immune interactions focusing on Type 17 and T regulatory helper subsets have been described. Thus, whether immune responses in this tissue are truly limited to a small number of antigenic triggers and effector functions remains to be fully elucidated. The small number of gut homeostatic CD4 T cell responses described thus far have been shown to primarily respond to specific commensal bacteria or dietary antigens (1, 2, 5-8): Among other examples, SFB induces cognate Th17 cells in the small intestine (9, 10), a consortium human commensal bacteria induces CD8b⁺ cells in the colon (11), and indices T and other effector cells in the Peyer's patches and lamina propria, respectively (12). Furthermore most regulatory T cells in the colon are induced in response to commensal or pathobiont species at homeostasis, providing critical regulatory functions (13, 14). Cognate immune responses to SFB help contain this commensal species in the intestine (15), but also have systemic impacts on the susceptibility to autoimmune disease (16, 17). Interestingly, despite presenting a classical Th17 effector profile, a subset of SFB-induced Th17 cells possess IL-10 secretion capabilities and suppress cognate immune responses without the expression of Foxp3 (18), suggesting immunoregulatory functions reminiscent of Tr1 cells. Whether these competing capabilities are unique to SFB-specific immune responses or a general hallmark of small intestinal immunity remains unknown. The description of SFB-specific Tr1-like cells in the small intestine was surprising, as this CD4⁺ T cell subset, characterized by abundant IL-10 secretion in the absence of expression, has only been described in the context of chronic antigen stimulation, such as chronic infection or cancer (19). The Tr1 cell program is controlled by a variety of transcription factors and upstream signaling pathways, including IL-27 signaling, MAF and AHR (20). AHR-ligands are abundant in the intestine, and MAF is a hallmark of other regulatory commensal-specific responses (21, 14). Furthermore, IL-27, which can induce both proinflammatory and immunoregulatory functions, is abundant in the small intestine (22, 23). This raises the possibility that the Tr1 program is a more general feature of small intestinal immunity, not uniquely restricted to SFB-specific responses. In this study we explore the breadth of CD4⁺ T cell responses in the small intestine, and uncover a previously uncharacterized CD4⁺T-bet⁺ T cell immune response that is dominant in this tissue. Unexpectedly, these SILP CD4⁺T-bet⁺ T cells are independent of the microbiota, maintaining a similar functional profile and shared antigen specificities in germ-free conditions. Instead, we reveal that dietary components drive the accumulation, function, and clonal selection of this T cell population. Finally, we show that, contrary to classical Th1 cells, SILP CD4⁺T-bet⁺ T cells adopt a Tr1 immunoregulatory functional program during activation, suggesting that this is a general feature of CD4⁺ T cell immunity in the small intestine wired towards immune regulation and tissue homeostasis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Intestinal immunity defends against enteric pathogens, mediates symbiotic relationships with the resident microbiota, and provides tolerance to food antigens, safeguarding critical nutrient absorption and barrier functions of this mucosal tissue. Despite the abundance of tissue resident activated T cells, their contributions to these various roles remains poorly understood. Here, we identify a dominant population of IL-10 producing, T-bet expressing CD4+ Tr1 T cells, residing in the small intestinal lamina propria at homeostasis. Remarkably, these intestinal Tr1 cells emerge at the time of weaning and accumulate independently of the microbiota displaying similar abundance, function and TCR repertoire under germ-free conditions. Instead, the small intestinal T-bet+ Tr1 program is driven and shaped by dietary antigens, and accumulates in a cDC1-IL-27 dependent manner. Upon activation, these cells robustly express IL-10 and multiple inhibitory receptors, establishing a distinct suppressive profile. Altogether, this work uncovers a previously unappreciated dominant player in homeostatic small intestinal immunity with the potential to play critical suppressive roles in this tissue, raising important implications for the understanding of immune regulation in the intestine.nnSIGNIFICANCE STATEMENT: Establishing immunological tolerance to self and environmental antigens is critical to preserve tissue homeostasis and function. In the intestine, both dietary and microbiota derived antigens are routinely encountered by the immune system, which deploys a variety of mechanisms to maintain tolerance to these innocuous antigens. Understanding how immunological tolerance is established is critical, a when this process goes awry it can lead to severe inflammatory and autoimmune diseases such as food allergy and inflammatory bowel disease. However, how tolerance is established in the intestine is still poorly understood. In this study we describe a novel dominant T cell population in the small intestine shaped by dietary components with the potential to play important roles in immune tolerance at this site. back # IntroductionBarrier surfaces such as the gut and skin represent the first line of defense against the environment. These organs must strike a delicate balance between providing protection against environmental and infectious agents, maintaining tissue function, and establishing a homeostatic symbiotic relationship with resident microbes collectively known as the microbiota (1). The immune system plays a critical role in establishing these dynamic and carefully regulated relationships, as evidenced by the large number of immune cells present at these sites. Of particular note, activated T cells are very abundant at barrier tissues, where they orchestrate immune effector functions geared towards these varied tasks (1, 2). In the small intestine, the intraepithelial compartment harbors innate like natural CD8aa⁺ IELs, many of which are self reactive; as well as CD4⁺CD8aa⁺ and CD8ab⁺ IELs responding to dietary and microbial antigens (3). The underlying lamina propria (SILP) harbors predominantly CD4⁺ T cells, which participate in responses to commensal-derived and dietary antigens (2, 4). Despite the abundance of small intestinal CD4 T cells, only a handful of cognate immune interactions focusing on Type 17 and T regulatory helper subsets have been described. Thus, whether immune responses in this tissue are truly limited to a small number of antigenic triggers and effector functions remains to be fully elucidated. The small number of gut homeostatic CD4 T cell responses described thus far have been shown to primarily respond to specific commensal bacteria or dietary antigens (1, 2, 5-8): Among other examples, SFB induces cognate Th17 cells in the small intestine (9, 10), a consortium human commensal bacteria induces CD8b⁺ cells in the colon (11), and indices T and other effector cells in the Peyer's patches and lamina propria, respectively (12). Furthermore most regulatory T cells in the colon are induced in response to commensal or pathobiont species at homeostasis, providing critical regulatory functions (13, 14). Cognate immune responses to SFB help contain this commensal species in the intestine (15), but also have systemic impacts on the susceptibility to autoimmune disease (16, 17). Interestingly, despite presenting a classical Th17 effector profile, a subset of SFB-induced Th17 cells possess IL-10 secretion capabilities and suppress cognate immune responses without the expression of Foxp3 (18), suggesting immunoregulatory functions reminiscent of Tr1 cells. Whether these competing capabilities are unique to SFB-specific immune responses or a general hallmark of small intestinal immunity remains unknown. The description of SFB-specific Tr1-like cells in the small intestine was surprising, as this CD4⁺ T cell subset, characterized by abundant IL-10 secretion in the absence of expression, has only been described in the context of chronic antigen stimulation, such as chronic infection or cancer (19). The Tr1 cell program is controlled by a variety of transcription factors and upstream signaling pathways, including IL-27 signaling, MAF and AHR (20). AHR-ligands are abundant in the intestine, and MAF is a hallmark of other regulatory commensal-specific responses (21, 14). Furthermore, IL-27, which can induce both proinflammatory and immunoregulatory functions, is abundant in the small intestine (22, 23). This raises the possibility that the Tr1 program is a more general feature of small intestinal immunity, not uniquely restricted to SFB-specific responses. In this study we explore the breadth of CD4⁺ T cell responses in the small intestine, and uncover a previously uncharacterized CD4⁺T-bet⁺ T cell immune response that is dominant in this tissue. Unexpectedly, these SILP CD4⁺T-bet⁺ T cells are independent of the microbiota, maintaining a similar functional profile and shared antigen specificities in germ-free conditions. Instead, we reveal that dietary components drive the accumulation, function, and clonal selection of this T cell population. Finally, we show that, contrary to classical Th1 cells, SILP CD4⁺T-bet⁺ T cells adopt a Tr1 immunoregulatory functional program during activation, suggesting that this is a general feature of CD4⁺ T cell immunity in the small intestine wired towards immune regulation and tissue homeostasis. |
Dimeglio, Chloé; Rakaawi, Mohamed El; Boineau, Jérôme; Smet, Clémentine De; Abravanel, Florence; Lhomme, Sébastien; Bardiaux, Laurent; Izopet, Jacques Increase in HEV IgG Seroprevalence During the Past Years in Southern France Journal Article In: J Med Virol, vol. 97, no. 7, pp. e70483, 2025, ISSN: 1096-9071. @article{pmid40673697,
title = {Increase in HEV IgG Seroprevalence During the Past Years in Southern France},
author = {Chloé Dimeglio and Mohamed El Rakaawi and Jérôme Boineau and Clémentine De Smet and Florence Abravanel and Sébastien Lhomme and Laurent Bardiaux and Jacques Izopet},
doi = {10.1002/jmv.70483},
issn = {1096-9071},
year = {2025},
date = {2025-07-01},
urldate = {2025-07-01},
journal = {J Med Virol},
volume = {97},
number = {7},
pages = {e70483},
abstract = {The sources and routes of HEV infections in industrialized countries are not fully defined. Occitanie in Southern France is an hyperendemic area but the relative extent of contaminated food and water consumption is unknown. We used validated assays to determine IgG and IgM seroprevalence among 3480 French blood donors living in Occitanie and compared the data with those obtained about twelve years ago. Epidemiological information was collected using a specific questionnaire. HEV IgG seroprevalence increased from 39.1% in 2011% to 47.8% in 2023. Unlike 12 years ago, the wastewater treatment method and tap water consumption were linked to HEV infection. Consumption of bottled water is now a risk factor for HEV infection. Overall IgM seroprevalence was 1.3%. The high prevalence of anti-HEV IgG in Occitanie cannot be explained by eating habits alone. Water consumption and treatment also appear to be important factors of HEV infections in Southern France.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The sources and routes of HEV infections in industrialized countries are not fully defined. Occitanie in Southern France is an hyperendemic area but the relative extent of contaminated food and water consumption is unknown. We used validated assays to determine IgG and IgM seroprevalence among 3480 French blood donors living in Occitanie and compared the data with those obtained about twelve years ago. Epidemiological information was collected using a specific questionnaire. HEV IgG seroprevalence increased from 39.1% in 2011% to 47.8% in 2023. Unlike 12 years ago, the wastewater treatment method and tap water consumption were linked to HEV infection. Consumption of bottled water is now a risk factor for HEV infection. Overall IgM seroprevalence was 1.3%. The high prevalence of anti-HEV IgG in Occitanie cannot be explained by eating habits alone. Water consumption and treatment also appear to be important factors of HEV infections in Southern France. |
Chaves, Beatriz; Silva, Juan Carlo Santos E; Nakaya, Helder; Socquet-Juglard, Nicolas; Bucciarelli, Florence; Prunier, Guilhèn; Almeida, Matheus V; Lacouture, Claire; Kari, Saniya; Astier, Anne L; Medeiros, Marco A; Silva, João H M; Liblau, Roland; Cotta-de-Almeida, Vinicius; Dupré, Loïc In vitro morphological profiling of T cells predicts clinical response to natalizumab therapy in patients with multiple sclerosis Journal Article In: Nat Commun, vol. 16, no. 1, pp. 5533, 2025, ISSN: 2041-1723. @article{pmid40595469,
title = {In vitro morphological profiling of T cells predicts clinical response to natalizumab therapy in patients with multiple sclerosis},
author = {Beatriz Chaves and Juan Carlo Santos E Silva and Helder Nakaya and Nicolas Socquet-Juglard and Florence Bucciarelli and Guilhèn Prunier and Matheus V Almeida and Claire Lacouture and Saniya Kari and Anne L Astier and Marco A Medeiros and João H M Silva and Roland Liblau and Vinicius Cotta-de-Almeida and Loïc Dupré},
doi = {10.1038/s41467-025-60224-3},
issn = {2041-1723},
year = {2025},
date = {2025-07-01},
urldate = {2025-07-01},
journal = {Nat Commun},
volume = {16},
number = {1},
pages = {5533},
abstract = {Despite the efficacy of natalizumab, which targets the integrin VLA-4, in treating multiple sclerosis (MS), approximately 35% patients with MS present evidence of disease activity two years after treatment initiation. Individual heterogeneity of leukocyte response to VLA-4 on natalizumab-mediated blockade may underlie disparities in treatment efficacy. Here we use a high-content cell imaging (HCI) pipeline to profile the in vitro effects of natalizumab on VLA-4-stimulated PBMCs from MS patients prior to natalizumab treatment. Unsupervised clustering of image data partially discriminates non-responder MS patients based on morphology, F-actin organization and signaling-related features in CD8 T cells. Furthermore, through a random forest approach, treatment response can be predicted with a performance of 92% for a discovery cohort and 88% for a validation cohort. Unfavorable treatment response is associated with a distinct actin remodeling response of natalizumab-exposed CD8 T cells and a residual ability of these cells to spread on VCAM-1. Our study thus unveils that CD8 T cells from individual MS patients display heterogeneous susceptibility to natalizumab in vitro and highlights the potential of HCI-based pretreatment monitoring to assist individualized treatment prescription.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Despite the efficacy of natalizumab, which targets the integrin VLA-4, in treating multiple sclerosis (MS), approximately 35% patients with MS present evidence of disease activity two years after treatment initiation. Individual heterogeneity of leukocyte response to VLA-4 on natalizumab-mediated blockade may underlie disparities in treatment efficacy. Here we use a high-content cell imaging (HCI) pipeline to profile the in vitro effects of natalizumab on VLA-4-stimulated PBMCs from MS patients prior to natalizumab treatment. Unsupervised clustering of image data partially discriminates non-responder MS patients based on morphology, F-actin organization and signaling-related features in CD8 T cells. Furthermore, through a random forest approach, treatment response can be predicted with a performance of 92% for a discovery cohort and 88% for a validation cohort. Unfavorable treatment response is associated with a distinct actin remodeling response of natalizumab-exposed CD8 T cells and a residual ability of these cells to spread on VCAM-1. Our study thus unveils that CD8 T cells from individual MS patients display heterogeneous susceptibility to natalizumab in vitro and highlights the potential of HCI-based pretreatment monitoring to assist individualized treatment prescription. |
Pignata, Aurora; Frieser, David; Gonzalez-Fierro, Carmen; Hsiao, Cheng-Chih; Engelenburg, Hendrik J; Alis, Marine; Fijalkow, Ilan; Cazaentre, Vincent; Nozeran, Lucie; Miranda-Capet, Romain; Dufourd, Eloïse; Vermeulen, Thaïs; Aïda, Amel; Coz, Carole Le; Gisbergen, Klaas Van; Blanchard, Nicolas; Hamann, Jörg; Smolders, Joost; Liblau, Roland S; Masson, Frederick Tissue-resident memory CD4 T cells infiltrate the CNS in progressive multiple sclerosis and contribute to chronic autoimmunity in mice Journal Article In: Sci Transl Med, vol. 17, no. 808, pp. eadp8109, 2025, ISSN: 1946-6242. @article{pmid40700520,
title = {Tissue-resident memory CD4 T cells infiltrate the CNS in progressive multiple sclerosis and contribute to chronic autoimmunity in mice},
author = {Aurora Pignata and David Frieser and Carmen Gonzalez-Fierro and Cheng-Chih Hsiao and Hendrik J Engelenburg and Marine Alis and Ilan Fijalkow and Vincent Cazaentre and Lucie Nozeran and Romain Miranda-Capet and Eloïse Dufourd and Thaïs Vermeulen and Amel Aïda and Carole Le Coz and Klaas Van Gisbergen and Nicolas Blanchard and Jörg Hamann and Joost Smolders and Roland S Liblau and Frederick Masson},
doi = {10.1126/scitranslmed.adp8109},
issn = {1946-6242},
year = {2025},
date = {2025-07-01},
urldate = {2025-07-01},
journal = {Sci Transl Med},
volume = {17},
number = {808},
pages = {eadp8109},
abstract = {Preventing T cell migration to the central nervous system (CNS) has remarkable therapeutic effects in relapsing-remitting multiple sclerosis (RRMS) but is poorly effective against the progressive form (PMS). Disability progression in PMS likely results from an interplay between smoldering local inflammation and neurodegeneration. The mechanisms sustaining the chronicity of PMS are poorly understood. Here, we investigated the potential role of tissue-resident memory CD4 T cells (CD4 Trm cells) in sustaining chronic CNS autoimmunity. We showed that CD4 Trm cells were present in the CNS of mice with chronic experimental autoimmune encephalomyelitis (EAE) and in brain tissues from persons with PMS. Using flow cytometry and immunohistofluorescence analysis, we revealed the presence of bona fide CD4 Trm cells expressing characteristic Trm cell surface markers, including CD69, CXCR6, P2RX7, and CD49a, in the CNS of mice with EAE and in the brains of persons with PMS. These T cells also expressed the transcription factor Hobit in mice with chronic EAE. Single-cell transcriptomic analysis uncovered the transcriptional heterogeneity and inflammatory potential of CD4 Trm cells, and, accordingly, these cells localized within CNS inflammatory lesions of mice with EAE and persons with PMS. Last, either genetic or pharmacological depletion of CD4 Trm cells combined with antibody-mediated depletion of the recirculating CD4 T cell compartment alleviated neurological signs during the chronic phase of EAE. Our results indicate that CD4 Trm cells contribute to maintain a chronic inflammatory state in the CNS and suggest that therapeutic strategies for PMS should consider targeting the CNS-resident T cell compartment.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Preventing T cell migration to the central nervous system (CNS) has remarkable therapeutic effects in relapsing-remitting multiple sclerosis (RRMS) but is poorly effective against the progressive form (PMS). Disability progression in PMS likely results from an interplay between smoldering local inflammation and neurodegeneration. The mechanisms sustaining the chronicity of PMS are poorly understood. Here, we investigated the potential role of tissue-resident memory CD4 T cells (CD4 Trm cells) in sustaining chronic CNS autoimmunity. We showed that CD4 Trm cells were present in the CNS of mice with chronic experimental autoimmune encephalomyelitis (EAE) and in brain tissues from persons with PMS. Using flow cytometry and immunohistofluorescence analysis, we revealed the presence of bona fide CD4 Trm cells expressing characteristic Trm cell surface markers, including CD69, CXCR6, P2RX7, and CD49a, in the CNS of mice with EAE and in the brains of persons with PMS. These T cells also expressed the transcription factor Hobit in mice with chronic EAE. Single-cell transcriptomic analysis uncovered the transcriptional heterogeneity and inflammatory potential of CD4 Trm cells, and, accordingly, these cells localized within CNS inflammatory lesions of mice with EAE and persons with PMS. Last, either genetic or pharmacological depletion of CD4 Trm cells combined with antibody-mediated depletion of the recirculating CD4 T cell compartment alleviated neurological signs during the chronic phase of EAE. Our results indicate that CD4 Trm cells contribute to maintain a chronic inflammatory state in the CNS and suggest that therapeutic strategies for PMS should consider targeting the CNS-resident T cell compartment. |
Morelli, María Paula; Martin, Candela; Pellegrini, Joaquín Miguel; Blanco, Federico; Bigi, Fabiana; Ciallella, Lorena; Musella, Rosa; Mieres, Adriana Rodriguez; de Casado, Graciela C; Palmero, Domingo Juan; García, Verónica Edith Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity Journal Article In: J Immunol, vol. 214, no. 6, pp. 1173–1186, 2025, ISSN: 1550-6606. @article{pmid40184042,
title = {Neutrophils from tuberculosis patients are polarized toward pro-inflammatory and anti-inflammatory phenotypes according to the disease severity},
author = {María Paula Morelli and Candela Martin and Joaquín Miguel Pellegrini and Federico Blanco and Fabiana Bigi and Lorena Ciallella and Rosa Musella and Adriana Rodriguez Mieres and Graciela C de Casado and Domingo Juan Palmero and Verónica Edith García},
doi = {10.1093/jimmun/vkaf010},
issn = {1550-6606},
year = {2025},
date = {2025-06-01},
urldate = {2025-06-01},
journal = {J Immunol},
volume = {214},
number = {6},
pages = {1173--1186},
abstract = {Neutrophils are the first line of defense against pathogens, combating them by using several antimicrobial mechanisms. These cells display a remarkable plasticity that can be molded by the different environments that neutrophils confront to protect the host, therefore presenting diverse phenotypes. Actually, pro- and anti-inflammatory neutrophils populations (N1- and N2-like phenotypes) have been described in cancer and inflammatory disorders. However, the identification of N1/N2 neutrophil subtypes in human intracellular bacterial diseases remains unexplored. Here, we characterized neutrophils from tuberculosis (TB) patients presenting distinct immunological status according to their disease severity. TB patients were classified as high or low responders (HR or LR) in accordance with their immunity against Mycobacterium tuberculosis (Mtb). Interestingly, by analyzing the phenotypic and functional characteristics of neutrophils from the two groups of TB patients we demonstrated that HR patient's neutrophils display a pro-inflammatory N1-like phenotype, whereas LR patient's neutrophils show an anti-inflammatory N2-like phenotype. Remarkably, whereas neutrophils from both groups of patients phagocytized MtbH37Rv strain equally, HR TB's neutrophils displayed a significantly increased ability to kill pathogenic Mtb as compared to neutrophils from LR TB patients that presented a diminished capacity of bacterial elimination. Together, our findings suggest the existence of different subtypes of neutrophils in TB patients according to their immune response to Mtb and disease severity, indicating that neutrophils might be promising targets for TB host-directed therapy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Neutrophils are the first line of defense against pathogens, combating them by using several antimicrobial mechanisms. These cells display a remarkable plasticity that can be molded by the different environments that neutrophils confront to protect the host, therefore presenting diverse phenotypes. Actually, pro- and anti-inflammatory neutrophils populations (N1- and N2-like phenotypes) have been described in cancer and inflammatory disorders. However, the identification of N1/N2 neutrophil subtypes in human intracellular bacterial diseases remains unexplored. Here, we characterized neutrophils from tuberculosis (TB) patients presenting distinct immunological status according to their disease severity. TB patients were classified as high or low responders (HR or LR) in accordance with their immunity against Mycobacterium tuberculosis (Mtb). Interestingly, by analyzing the phenotypic and functional characteristics of neutrophils from the two groups of TB patients we demonstrated that HR patient's neutrophils display a pro-inflammatory N1-like phenotype, whereas LR patient's neutrophils show an anti-inflammatory N2-like phenotype. Remarkably, whereas neutrophils from both groups of patients phagocytized MtbH37Rv strain equally, HR TB's neutrophils displayed a significantly increased ability to kill pathogenic Mtb as compared to neutrophils from LR TB patients that presented a diminished capacity of bacterial elimination. Together, our findings suggest the existence of different subtypes of neutrophils in TB patients according to their immune response to Mtb and disease severity, indicating that neutrophils might be promising targets for TB host-directed therapy. |
Pons, Carole; Lachambre, Simon; Goudouneche, Dominique; Simon, Michel; Leprince, Corinne Rab27B GTPase Regulates Late Steps of Lamellar Body Trafficking Journal Article In: J Invest Dermatol, 2025, ISSN: 1523-1747. @article{pmid40473201,
title = {Rab27B GTPase Regulates Late Steps of Lamellar Body Trafficking},
author = {Carole Pons and Simon Lachambre and Dominique Goudouneche and Michel Simon and Corinne Leprince},
doi = {10.1016/j.jid.2025.05.024},
issn = {1523-1747},
year = {2025},
date = {2025-06-01},
urldate = {2025-06-01},
journal = {J Invest Dermatol},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
