@article{Starkl2024,

title = {Mast cell–derived BH4 and serotonin are critical mediators of postoperative pain},

author = {Philipp Starkl and Gustav Jonsson and Tyler Artner and Bruna Lenfers Turnes and Laura-Marie Gail and Tiago Oliveira and Aakanksha Jain and Nadine Serhan and Karel Stejskal and Karin Lakovits and Anastasiya Hladik and Meilin An and Keith M. Channon and Hail Kim and Thomas Köcher and Wolfgang Weninger and Georg Stary and Sylvia Knapp and Victoria Klang and Nicolas Gaudenzio and Clifford J. Woolf and Shweta Tikoo and Rohit Jain and Josef M. Penninger and Shane J.F. Cronin},

url = {https://www-science-org.proxy.insermbiblio.inist.fr/doi/10.1126/sciimmunol.adh0545},

doi = {10.1126/sciimmunol.adh0545},

year  = {2024},

date = {2024-08-23},

urldate = {2024-08-23},

journal = {Science Immunology},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Scholaert2024,

title = {Multimodal profiling of biostabilized human skin modules reveals a coordinated ecosystem response to injected mRNA-1273 COVID-19 vaccine},

author = {Scholaert M; Peries M; Braun E; Martin J; Serhan N; Loste A;, Bruner A; Basso L; Chaput B; Merle E; Descargues P; Pagès E; Gaudenzio N},

doi = {https://doi.org/10.1111/all.16273},

year  = {2024},

date = {2024-08-19},

urldate = {2024-08-19},

journal = {Allergy},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39110619,

title = {Enkephalin-mediated modulation of basal somatic sensitivity by regulatory T cells in mice},

author = {Nicolas Aubert and Madeleine Purcarea and Julien Novarino and Julien Schopp and Alexis Audibert and Wangtianrui Li and Marie Fornier and Léonie Cagnet and Marie Naturel and Armanda Casrouge and Marie-Caroline Dieu-Nosjean and Nicolas Blanchard and Gilles Dietrich and Cedric Peirs and Gilles Marodon},

doi = {10.7554/eLife.91359},

issn = {2050-084X},

year  = {2024},

date = {2024-08-01},

journal = {Elife},

volume = {13},

abstract = {CD4CD25Foxp3 regulatory T cells (Treg) have been implicated in pain modulation in various inflammatory conditions. However, whether Treg cells hamper pain at steady state and by which mechanism is still unclear. From a meta-analysis of the transcriptomes of murine Treg and conventional T cells (Tconv), we observe that the proenkephalin gene (), encoding the precursor of analgesic opioid peptides, ranks among the top 25 genes most enriched in Treg cells. We then present various evidence suggesting that  is regulated in part by members of the Tumor Necrosis Factor Receptor (TNFR) family and the transcription factor Basic leucine zipper transcription faatf-like (BATF). Using mice in which the promoter activity of  can be tracked with a fluorescent reporter, we also show that  expression is mostly detected in Treg and activated Tconv in non-inflammatory conditions in the colon and skin. Functionally, Treg cells proficient or deficient for  suppress equally well the proliferation of effector T cells in vitro and autoimmune colitis in vivo. In contrast, inducible ablation of  in Treg leads to heat hyperalgesia in both male and female mice. Overall, our results indicate that Treg might play a key role at modulating basal somatic sensitivity in mice through the production of analgesic opioid peptides.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Voisin2024,

title = {Anaplastic lymphoma kinase as a new therapeutic target in inflammatory itch},

author = {Tiphaine Voisin and Elodie Labit and Nicolas Gaudenzio and Lilian Basso},

url = {https://onlinelibrary-wiley-com.proxy.insermbiblio.inist.fr/doi/full/10.1111/all.16260},

doi = { https://doi-org.proxy.insermbiblio.inist.fr/10.1111/all.16260},

year  = {2024},

date = {2024-07-26},

journal = {Allergy},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wollam2024,

title = {Inhibition of Mast Cell Degranulation by Novel Small Molecule MRGPRX2 Antagonists},

author = {Joshua Wollam and Michelle Solomon and Christiane Villescaz and Marion Lanier and Samantha Evans and Corinne Bacon and David Freeman and Alexis Vasquez and Alan Vest and Jim Napora and Brittney Charlot and Christine Cavarlez and Andrew Kim and Lisa Dvorak and Brandon Selfridge and Liming Huang and Andres Nevarez and Harry Dedman and Jennifer Brooks and Stefan Frischbutter and Martin Metz and Nadine

Serhan and Nicolas Gaudenzio and Gregg Timony and Esther Martinborough and Marcus F. Boehm and Veena Viswanath},

url = {https://www.jacionline.org/article/S0091-6749(24)00675-4/fulltext},

year  = {2024},

date = {2024-07-04},

urldate = {2024-07-04},

booktitle = {Journal of Allergy and Clinical Immunology},

journal = {Journal of Allergy and Clinical Immunology},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cadot_new_2024,

title = {New pharmacodynamic parameters linked with ibrutinib responses in chronic lymphocytic leukemia: Prospective study in real-world patients and mathematical modeling},

author = {Sarah Cadot and Chloe Audebert and Charlotte Dion and Soleakhena Ken and Loic Dupré and Laetitia Largeaud and Camille Laurent and Loic Ysebaert and Fabien Crauste and Anne Quillet-Mary},

doi = {10.1371/journal.pmed.1004430},

issn = {1549-1676},

year  = {2024},

date = {2024-07-01},

urldate = {2024-07-01},

journal = {PLoS medicine},

volume = {21},

number = {7},

pages = {e1004430},

abstract = {BACKGROUND: One of the first clinical observations of ibrutinib activity in the treatment of chronic lymphocytic leukemia (CLL) is a rapid decline in lymph nodes size. This phenomenon is accompanied by an hyperlymphocytosis, either transient or prolonged, which is associated with distinct clinical responses and thus has an impact on long-term outcomes. Understanding which factors determine distinct disease courses upon ibrutinib treatment remains a scientific challenge. METHODS AND FINDINGS: From 2016 to 2021, we conducted a longitudinal and observational study in 2 cohorts of patients with chronic lymphocytic leukemia (CLL) (cohort 1},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{fusaro_mechanisms_2024,

title = {Mechanisms underlying skin inflammation of DOCK8 deficiency},

author = {Mathieu Fusaro and Loïc Dupré},

doi = {10.1016/j.jaci.2024.04.026},

issn = {1097-6825},

year  = {2024},

date = {2024-07-01},

urldate = {2024-07-01},

journal = {The Journal of Allergy and Clinical Immunology},

volume = {154},

number = {1},

pages = {88–90},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38834865,

title = {Cell shape sensing licenses dendritic cells for homeostatic migration to lymph nodes},

author = {Zahraa Alraies and Claudia A Rivera and Maria-Graciela Delgado and Doriane Sanséau and Mathieu Maurin and Roberto Amadio and Giulia Maria Piperno and Garett Dunsmore and Aline Yatim and Livia Lacerda Mariano and Anna Kniazeva and Vincent Calmettes and Pablo J Sáez and Alice Williart and Henri Popard and Matthieu Gratia and Olivier Lamiable and Aurélie Moreau and Zoé Fusilier and Lou Crestey and Benoit Albaud and Patricia Legoix and Anne S Dejean and Anne-Louise Le Dorze and Hideki Nakano and Donald N Cook and Toby Lawrence and Nicolas Manel and Federica Benvenuti and Florent Ginhoux and Hélène D Moreau and Guilherme P F Nader and Matthieu Piel and Ana-Maria Lennon-Duménil},

doi = {10.1038/s41590-024-01856-3},

issn = {1529-2916},

year  = {2024},

date = {2024-07-01},

urldate = {2024-07-01},

journal = {Nat Immunol},

volume = {25},

number = {7},

pages = {1193--1206},

abstract = {Immune cells experience large cell shape changes during environmental patrolling because of the physical constraints that they encounter while migrating through tissues. These cells can adapt to such deformation events using dedicated shape-sensing pathways. However, how shape sensing affects immune cell function is mostly unknown. Here, we identify a shape-sensing mechanism that increases the expression of the chemokine receptor CCR7 and guides dendritic cell migration from peripheral tissues to lymph nodes at steady state. This mechanism relies on the lipid metabolism enzyme cPLA, requires nuclear envelope tensioning and is finely tuned by the ARP2/3 actin nucleation complex. We also show that this shape-sensing axis reprograms dendritic cell transcription by activating an IKKβ-NF-κB-dependent pathway known to control their tolerogenic potential. These results indicate that cell shape changes experienced by immune cells can define their migratory behavior and immunoregulatory properties and reveal a contribution of the physical properties of tissues to adaptive immunity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bettamin2024b,

title = {Real‐Time and High‐Resolution Monitoring of Neuronal Electrical Activity and pH Variations Based on the Co‐Integration of Nanoelectrodes and Chem‐FinFETs},

author = {Luca Bettamin and Fabrice Mathieu and Florent H. Marty and Marie Charline Blatche and Daniel Gonzalez‐Dunia and Elsa Suberbielle and Guilhem Larrieu},

doi = {10.1002/smll.202309055},

issn = {1613-6829},

year  = {2024},

date = {2024-07-00},

urldate = {2024-07-00},

journal = {Small},

volume = {20},

number = {27},

publisher = {Wiley},

abstract = {<jats:title>Abstract</jats:title><jats:p>Developing new approaches amenable to the measurement of neuronal physiology in real‐time is a very active field of investigation, as it will offer improved methods to assess the impact of diverse insults on neuronal homeostasis. Here, the development of an in vitro bio platform is reported which can record the electrical activity of cultured primary rat cortical neurons with extreme sensitivity, while simultaneously tracking the localized changes in the pH of the culture medium. This bio platform features passive vertical nanoprobes with ultra‐high signal resolution (several mV amplitude ranges) and Chem‐FinFETs (pH sensitivity of sub‐0.1 pH units), covering an area as little as a neuronal soma. These multi‐sensing units are arranged in an array to probe both chemically and electrically an equivalent surface of ≈ 0.5 mm<jats:sup>2</jats:sup>. A homemade setup is also developed which allows recording of multiplexed data in real‐time (10 ps range) from the active chem‐sensors and passive electrodes and which is used to operate the platform. Finally, a proof‐of‐concept is presented for a neuro‐relevant application, by investigating the effect on neuronal activity of Amyloid beta oligomers, the main toxic peptide in Alzheimer's Disease, which reveals that exposure to amyloid beta oligomers modify the amplitude, but not the frequency, of neuronal firing, without any detectable changes in pH values along this process.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bettamin2024,

title = {Real‐Time and High‐Resolution Monitoring of Neuronal Electrical Activity and pH Variations Based on the Co‐Integration of Nanoelectrodes and Chem‐FinFETs},

author = {Luca Bettamin and Fabrice Mathieu and Florent H. Marty and Marie Charline Blatche and Daniel Gonzalez‐Dunia and Elsa Suberbielle and Guilhem Larrieu},

doi = {10.1002/smll.202309055},

issn = {1613-6829},

year  = {2024},

date = {2024-07-00},

journal = {Small},

volume = {20},

number = {27},

publisher = {Wiley},

abstract = {AbstractDeveloping new approaches amenable to the measurement of neuronal physiology in real‐time is a very active field of investigation, as it will offer improved methods to assess the impact of diverse insults on neuronal homeostasis. Here, the development of an in vitro bio platform is reported which can record the electrical activity of cultured primary rat cortical neurons with extreme sensitivity, while simultaneously tracking the localized changes in the pH of the culture medium. This bio platform features passive vertical nanoprobes with ultra‐high signal resolution (several mV amplitude ranges) and Chem‐FinFETs (pH sensitivity of sub‐0.1 pH units), covering an area as little as a neuronal soma. These multi‐sensing units are arranged in an array to probe both chemically and electrically an equivalent surface of ≈ 0.5 mm2. A homemade setup is also developed which allows recording of multiplexed data in real‐time (10 ps range) from the active chem‐sensors and passive electrodes and which is used to operate the platform. Finally, a proof‐of‐concept is presented for a neuro‐relevant application, by investigating the effect on neuronal activity of Amyloid beta oligomers, the main toxic peptide in Alzheimer's Disease, which reveals that exposure to amyloid beta oligomers modify the amplitude, but not the frequency, of neuronal firing, without any detectable changes in pH values along this process.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38838017c,

title = {Protective function and differentiation cues of brain-resident CD8+ T cells during surveillance of latent  infection},

author = {Rémi Porte and Marcy Belloy and Alexis Audibert and Emilie Bassot and Amel Aïda and Marine Alis and Romain Miranda-Capet and Aurélie Jourdes and Klaas P J M van Gisbergen and Frédérick Masson and Nicolas Blanchard},

doi = {10.1073/pnas.2403054121},

issn = {1091-6490},

year  = {2024},

date = {2024-06-01},

journal = {Proc Natl Acad Sci U S A},

volume = {121},

number = {24},

pages = {e2403054121},

abstract = {Chronic  infection induces brain-resident CD8+ T cells (bTr), but the protective functions and differentiation cues of these cells remain undefined. Here, we used a mouse model of latent infection by  leading to effective CD8+ T cell-mediated parasite control. Thanks to antibody depletion approaches, we found that peripheral circulating CD8+ T cells are dispensable for brain parasite control during chronic stage, indicating that CD8+ bTr are able to prevent brain parasite reactivation. We observed that the retention markers CD69, CD49a, and CD103 are sequentially acquired by brain parasite-specific CD8+ T cells throughout infection and that a majority of CD69/CD49a/CD103 triple-positive (TP) CD8+ T cells also express Hobit, a transcription factor associated with tissue residency. This TP subset develops in a CD4+ T cell-dependent manner and is associated with effective parasite control during chronic stage. Conditional invalidation of Transporter associated with Antigen Processing (TAP)-mediated major histocompatibility complex (MHC) class I presentation showed that presentation of parasite antigens by glutamatergic neurons and microglia regulates the differentiation of CD8+ bTr into TP cells. Single-cell transcriptomic analyses revealed that resistance to encephalitis is associated with the expansion of stem-like subsets of CD8+ bTr. In summary, parasite-specific brain-resident CD8+ T cells are a functionally heterogeneous compartment which autonomously ensure parasite control during  latent infection and which differentiation is shaped by neuronal and microglial MHC I presentation. A more detailed understanding of local T cell-mediated immune surveillance of this common parasite is needed for harnessing brain-resident CD8+ T cells in order to enhance control of chronic brain infections.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38838017b,

title = {Protective function and differentiation cues of brain-resident CD8+ T cells during surveillance of latent  infection},

author = {Rémi Porte and Marcy Belloy and Alexis Audibert and Emilie Bassot and Amel Aïda and Marine Alis and Romain Miranda-Capet and Aurélie Jourdes and Klaas P J M van Gisbergen and Frédérick Masson and Nicolas Blanchard},

doi = {10.1073/pnas.2403054121},

issn = {1091-6490},

year  = {2024},

date = {2024-06-01},

urldate = {2024-06-01},

journal = {Proc Natl Acad Sci U S A},

volume = {121},

number = {24},

pages = {e2403054121},

abstract = {Chronic  infection induces brain-resident CD8+ T cells (bTr), but the protective functions and differentiation cues of these cells remain undefined. Here, we used a mouse model of latent infection by  leading to effective CD8+ T cell-mediated parasite control. Thanks to antibody depletion approaches, we found that peripheral circulating CD8+ T cells are dispensable for brain parasite control during chronic stage, indicating that CD8+ bTr are able to prevent brain parasite reactivation. We observed that the retention markers CD69, CD49a, and CD103 are sequentially acquired by brain parasite-specific CD8+ T cells throughout infection and that a majority of CD69/CD49a/CD103 triple-positive (TP) CD8+ T cells also express Hobit, a transcription factor associated with tissue residency. This TP subset develops in a CD4+ T cell-dependent manner and is associated with effective parasite control during chronic stage. Conditional invalidation of Transporter associated with Antigen Processing (TAP)-mediated major histocompatibility complex (MHC) class I presentation showed that presentation of parasite antigens by glutamatergic neurons and microglia regulates the differentiation of CD8+ bTr into TP cells. Single-cell transcriptomic analyses revealed that resistance to encephalitis is associated with the expansion of stem-like subsets of CD8+ bTr. In summary, parasite-specific brain-resident CD8+ T cells are a functionally heterogeneous compartment which autonomously ensure parasite control during  latent infection and which differentiation is shaped by neuronal and microglial MHC I presentation. A more detailed understanding of local T cell-mediated immune surveillance of this common parasite is needed for harnessing brain-resident CD8+ T cells in order to enhance control of chronic brain infections.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38838017,

title = {Protective function and differentiation cues of brain-resident CD8+ T cells during surveillance of latent  infection},

author = {Rémi Porte and Marcy Belloy and Alexis Audibert and Emilie Bassot and Amel Aïda and Marine Alis and Romain Miranda-Capet and Aurélie Jourdes and Klaas P J M van Gisbergen and Frédérick Masson and Nicolas Blanchard},

doi = {10.1073/pnas.2403054121},

issn = {1091-6490},

year  = {2024},

date = {2024-06-01},

journal = {Proc Natl Acad Sci U S A},

volume = {121},

number = {24},

pages = {e2403054121},

abstract = {Chronic  infection induces brain-resident CD8+ T cells (bTr), but the protective functions and differentiation cues of these cells remain undefined. Here, we used a mouse model of latent infection by  leading to effective CD8+ T cell-mediated parasite control. Thanks to antibody depletion approaches, we found that peripheral circulating CD8+ T cells are dispensable for brain parasite control during chronic stage, indicating that CD8+ bTr are able to prevent brain parasite reactivation. We observed that the retention markers CD69, CD49a, and CD103 are sequentially acquired by brain parasite-specific CD8+ T cells throughout infection and that a majority of CD69/CD49a/CD103 triple-positive (TP) CD8+ T cells also express Hobit, a transcription factor associated with tissue residency. This TP subset develops in a CD4+ T cell-dependent manner and is associated with effective parasite control during chronic stage. Conditional invalidation of Transporter associated with Antigen Processing (TAP)-mediated major histocompatibility complex (MHC) class I presentation showed that presentation of parasite antigens by glutamatergic neurons and microglia regulates the differentiation of CD8+ bTr into TP cells. Single-cell transcriptomic analyses revealed that resistance to encephalitis is associated with the expansion of stem-like subsets of CD8+ bTr. In summary, parasite-specific brain-resident CD8+ T cells are a functionally heterogeneous compartment which autonomously ensure parasite control during  latent infection and which differentiation is shaped by neuronal and microglial MHC I presentation. A more detailed understanding of local T cell-mediated immune surveillance of this common parasite is needed for harnessing brain-resident CD8+ T cells in order to enhance control of chronic brain infections.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38713628,

title = {THEMIS promotes T cell development and maintenance by rising the signaling threshold of the inhibitory receptor BTLA},

author = {Suzanne Mélique and Aurélie Vadel and Nelly Rouquié and Cui Yang and Cyrielle Bories and Coline Cotineau and Abdelhadi Saoudi and Nicolas Fazilleau and Renaud Lesourne},

doi = {10.1073/pnas.2318773121},

issn = {1091-6490},

year  = {2024},

date = {2024-05-01},

urldate = {2024-05-01},

journal = {Proc Natl Acad Sci U S A},

volume = {121},

number = {20},

pages = {e2318773121},

abstract = {The current paradigm about the function of T cell immune checkpoints is that these receptors switch on inhibitory signals upon cognate ligand interaction. We here revisit this simple switch model and provide evidence that the T cell lineage protein THEMIS enhances the signaling threshold at which the immune checkpoint BTLA (B- and T-lymphocyte attenuator) represses T cell responses. THEMIS is recruited to the cytoplasmic domain of BTLA and blocks its signaling capacity by promoting/stabilizing the oxidation of the catalytic cysteine of the tyrosine phosphatase SHP-1. In contrast, THEMIS has no detectable effect on signaling pathways regulated by PD-1 (Programmed cell death protein 1), which depend mainly on the tyrosine phosphatase SHP-2. BTLA inhibitory signaling is tuned according to the THEMIS expression level, making CD8+ T cells more resistant to BTLA-mediated inhibition than CD4+ T cells. In the absence of THEMIS, the signaling capacity of BTLA is exacerbated, which results in the attenuation of signals driven by the T cell antigen receptor and by receptors for IL-2 and IL-15, consequently hampering thymocyte positive selection and peripheral CD8+ T cell maintenance. By characterizing the pivotal role of THEMIS in restricting the transmission of BTLA signals, our study suggests that immune checkpoint operability is conditioned by intracellular signal attenuators.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{marrocco_positive_2024,

title = {Positive regulation of Vav1 by Themis controls CD4 T cell pathogenicity in a mouse model of central nervous system inflammation},

author = {Remi Marrocco and Isabelle Bernard and Emeline Joulia and Rebecca Barascud and Anne S. Dejean and Renaud Lesourne and Abdelhadi Saoudi},

doi = {10.1007/s00018-024-05203-5},

issn = {1420-9071},

year  = {2024},

date = {2024-04-01},

urldate = {2024-04-01},

journal = {Cellular and molecular life sciences: CMLS},

volume = {81},

number = {1},

pages = {161},

abstract = {The susceptibility to autoimmune diseases is conditioned by the association of modest genetic alterations which altogether weaken self-tolerance. The mechanism whereby these genetic interactions modulate T-cell pathogenicity remains largely uncovered. Here, we investigated the epistatic interaction of two interacting proteins involved in T Cell Receptor signaling and which were previously associated with the development of Multiple Sclerosis. To this aim, we used mice expressing an hypomorphic variant of Vav1 (Vav1R63W), combined with a T cell-conditional deletion of Themis. We show that the combined mutations in Vav1 and Themis induce a strong attenuation of the severity of Experimental Autoimmune Encephalomyelitis (EAE), contrasting with the moderate effect of the single mutation in each of those two proteins. This genotype-dependent gradual decrease of EAE severity correlates with decreased quantity of phosphorylated Vav1 in CD4 T cells, establishing that Themis promotes the development of encephalitogenic Tconv response by enhancing Vav1 activity. We also show that the cooperative effect of Themis and Vav1 on EAE severity is independent of regulatory T cells and unrelated to the impact of Themis on thymic selection. Rather, it results from decreased production of pro-inflammatory cytokines (IFN-γ, IL-17, TNF and GM-CSF) and reduced T cell infiltration in the CNS. Together, our results provide a rationale to study combination of related genes, in addition to single gene association, to better understand the genetic bases of human diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38565808,

title = {Positive regulation of Vav1 by Themis controls CD4 T cell pathogenicity in a mouse model of central nervous system inflammation},

author = {Remi Marrocco and Isabelle Bernard and Emeline Joulia and Rebecca Barascud and Anne S Dejean and Renaud Lesourne and Abdelhadi Saoudi},

doi = {10.1007/s00018-024-05203-5},

issn = {1420-9071},

year  = {2024},

date = {2024-04-01},

urldate = {2024-04-01},

journal = {Cell Mol Life Sci},

volume = {81},

number = {1},

pages = {161},

abstract = {The susceptibility to autoimmune diseases is conditioned by the association of modest genetic alterations which altogether weaken self-tolerance. The mechanism whereby these genetic interactions modulate T-cell pathogenicity remains largely uncovered. Here, we investigated the epistatic interaction of two interacting proteins involved in T Cell Receptor signaling and which were previously associated with the development of Multiple Sclerosis. To this aim, we used mice expressing an hypomorphic variant of Vav1 (Vav1), combined with a T cell-conditional deletion of Themis. We show that the combined mutations in Vav1 and Themis induce a strong attenuation of the severity of Experimental Autoimmune Encephalomyelitis (EAE), contrasting with the moderate effect of the single mutation in each of those two proteins. This genotype-dependent gradual decrease of EAE severity correlates with decreased quantity of phosphorylated Vav1 in CD4 T cells, establishing that Themis promotes the development of encephalitogenic Tconv response by enhancing Vav1 activity. We also show that the cooperative effect of Themis and Vav1 on EAE severity is independent of regulatory T cells and unrelated to the impact of Themis on thymic selection. Rather, it results from decreased production of pro-inflammatory cytokines (IFN-γ, IL-17, TNF and GM-CSF) and reduced T cell infiltration in the CNS. Together, our results provide a rationale to study combination of related genes, in addition to single gene association, to better understand the genetic bases of human diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{kamnev_coordinated_2024,

title = {Coordinated ARP2/3 and glycolytic activities regulate the morphological and functional fitness of human CD8+ T cells},

author = {Anton Kamnev and Tanvi Mehta and Matthias Wielscher and Beatriz Chaves and Claire Lacouture and Anna-Katharina Mautner and Lisa E. Shaw and Michael Caldera and Jörg Menche and Wolfgang P. Weninger and Matthias Farlik and Kaan Boztug and Loïc Dupré},

doi = {10.1016/j.celrep.2024.113853},

issn = {2211-1247},

year  = {2024},

date = {2024-03-01},

urldate = {2024-03-01},

journal = {Cell Reports},

volume = {43},

number = {3},

pages = {113853},

abstract = {Actin cytoskeleton remodeling sustains the ability of cytotoxic T cells to search for target cells and eliminate them. We here investigated the relationship between energetic status, actin remodeling, and functional fitness in human CD8+ effector T cells. Cell spreading during migration or immunological synapse assembly mirrored cytotoxic activity. Morphological and functional fitness were boosted by interleukin-2 (IL-2), which also stimulated the transcription of glycolytic enzymes, actin isoforms, and actin-related protein (ARP)2/3 complex subunits. This molecular program scaled with F-actin content and cell spreading. Inhibiting glycolysis impaired F-actin remodeling at the lamellipodium, chemokine-driven motility, and adhesion, while mitochondrial oxidative phosphorylation blockade impacted cell elongation during confined migration. The severe morphological and functional defects of ARPC1B-deficient T cells were only partially corrected by IL-2, emphasizing ARP2/3-mediated actin polymerization as a crucial energy state integrator. The study therefore underscores the tight coordination between metabolic and actin remodeling programs to sustain the cytotoxic activity of CD8+ T cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{rey-barroso_lymphocyte_2024,

title = {Lymphocyte migration and retention properties affected by ibrutinib in chronic lymphocytic leukemia},

author = {Javier Rey-Barroso and Alice Munaretto and Nelly Rouquié and Aurélie Mougel and Malika Chassan and Sébastien Gadat and Océane Dewingle and Renaud Poincloux and Sarah Cadot and Loïc Ysebaert and Anne Quillet-Mary and Loïc Dupré},

doi = {10.3324/haematol.2022.282466},

issn = {1592-8721},

year  = {2024},

date = {2024-03-01},

urldate = {2024-03-01},

journal = {Haematologica},

volume = {109},

number = {3},

pages = {809–823},

abstract = {The Bruton tyrosine kinase (BTK) inhibitor ibrutinib is widely used for treatment of patients with relapsed/refractory or treatment-naïve chronic lymphocytic leukemia (CLL). A prominent effect of ibrutinib is to disrupt the retention of CLL cells from supportive lymphoid tissues, by altering BTK-dependent adhesion and migration. To further explore the mechanism of action of ibrutinib and its potential impact on non-leukemic cells, we quantified multiple motility and adhesion parameters of human primary CLL cells and non-leukemic lymphoid cells. In vitro, ibrutinib affected CCL19-, CXCL12- and CXCL13-evoked migration behavior of CLL cells and non-neoplastic lymphocytes, by reducing both motility speed and directionality. De-phosphorylation of BTK induced by ibrutinib in CLL cells was associated with defective polarization over fibronectin and inability to assemble the immunological synapse upon B-cell receptor engagement. In patients' samples collected during a 6-month monitoring of therapy, chemokine-evoked migration was repressed in CLL cells and marginally reduced in T cells. This was accompanied by profound modulation of the expression of chemokine receptors and adhesion molecules. Remarkably, the relative expression of the receptors governing lymph node entry (CCR7) versus exit (S1PR1) stood out as a reliable predictive marker of the clinically relevant treatment-induced lymphocytosis. Together, our data reveal a multifaceted modulation of motility and adhesive properties of ibrutinib on both CLL leukemic cell and T-cell populations and point to intrinsic differences in CLL recirculation properties as an underlying cause for variability in treatment response.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Santamaria2024,

title = {The type 1 diabetes susceptibility locus Idd5 favours robust neonatal development of highly autoreactive regulatory T cells in the NOD mouse},

author = {Jérémy C. Santamaria and Sylvia Vuillier and Ariel O. Galindo-Albarrán and Sarah Castan and Claire Detraves and Olivier P. Joffre and Paola Romagnoli and Joost P. M. van Meerwijk},

doi = {10.3389/fimmu.2024.1358459},

issn = {1664-3224},

year  = {2024},

date = {2024-02-09},

journal = {Front. Immunol.},

volume = {15},

publisher = {Frontiers Media SA},

abstract = {Regulatory T lymphocytes expressing the transcription factor Foxp3 (Tregs) play an important role in the prevention of autoimmune diseases and other immunopathologies. Aberrations in Treg-mediated immunosuppression are therefore thought to be involved in the development of autoimmune pathologies, but few have been documented. Recent reports indicated a central role for Tregs developing during the neonatal period in the prevention of autoimmune pathology. We therefore investigated the development of Tregs in neonatal NOD mice, an important animal model for autoimmune type 1 diabetes. Surprisingly, we found that, as compared with seven other commonly studied inbred mouse strains, in neonatal NOD mice, exceptionally large proportions of developing Tregs express high levels of GITR and PD-1. The latter phenotype was previously associated with high Treg autoreactivity in C57BL/6 mice, which we here confirm for NOD animals. The proportions of newly developing GITRhighPD-1+ Tregs rapidly drop during the first week of age. A genome-wide genetic screen indicated the involvement of several diabetes susceptibility loci in this trait. Analysis of a congenic mouse strain confirmed that Idd5 contributes to the genetic control of GITRhighPD-1+ Treg development in neonates. Our data thus demonstrate an intriguing and paradoxical correlation between an idiosyncrasy in Treg development in NOD mice and their susceptibility to type 1 diabetes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Joulia2024,

title = {Eomes-dependent mitochondrial regulation promotes survival of pathogenic CD4+ T cells during inflammation},

author = {Emeline Joulia and Michaël F. Michieletto and Arantxa Agesta and Cindy Peillex and Virginie Girault and Anne-Louise Le Dorze and Romain Peroceschi and Florence Bucciarelli and Marion Szelechowski and Adeline Chaubet and Nawad Hakim and Rémi Marrocco and Emeline Lhuillier and Manuel Lebeurrier and Rafael J. Argüello and Abdelhadi Saoudi and Hicham El Costa and Veronique Adoue and Thierry Walzer and Jean-Emmanuel Sarry and Anne S. Dejean},

doi = {10.1084/jem.20230449},

issn = {1540-9538},

year  = {2024},

date = {2024-02-05},

volume = {221},

number = {2},

publisher = {Rockefeller University Press},

abstract = {The mechanisms whereby Eomes controls tissue accumulation of T cells and strengthens inflammation remain ill-defined. Here, we show that Eomes deletion in antigen-specific CD4+ T cells is sufficient to protect against central nervous system (CNS) inflammation. While Eomes is dispensable for the initial priming of CD4+ T cells, it is required for long-term maintenance of CNS-infiltrating CD4+ T cells. We reveal that the impact of Eomes on effector CD4+ T cell longevity is associated with sustained expression of multiple genes involved in mitochondrial organization and functions. Accordingly, epigenetic studies demonstrate that Eomes supports mitochondrial function by direct binding to either metabolism-associated genes or mitochondrial transcriptional modulators. Besides, the significance of these findings was confirmed in CD4+ T cells from healthy donors and multiple sclerosis patients. Together, our data reveal a new mechanism by which Eomes promotes severity and chronicity of inflammation via the enhancement of CD4+ T cell mitochondrial functions and resistance to stress-induced cell death.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}