@article{RN2480,

title = {Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis},

author = {Chi, L. and Liu, C. and Gribonika, I. and Gschwend, J. and Corral, D. and Han, S. J. and Lim, A. I. and Rivera, C. A. and Link, V. M. and Wells, A. C. and Bouladoux, N. and Collins, N. and Lima-Junior, D. S. and Enamorado, M. and Rehermann, B. and Laffont, S. and Guery, J. C. and Tussiwand, R. and Schneider, C. and Belkaid, Y.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/38574174},

doi = {10.1126/science.adk6200},

issn = {1095-9203 (Electronic) 0036-8075 (Linking)},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {Science},

volume = {384},

number = {6692},

pages = {eadk6200},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN2122,

title = {The Prevalence Of Osteoporosis Is Low in Adult Cutaneous Mastocytosis Patients},

author = {Y. Degboe and M. Severino-Freire and G. Couture and P. A. Apoil and N. Gaudenzio and O. Hermine and A. Ruyssen-Witrand and C. Paul and M. Laroche and A. Constantin and C. B. Livideanu},

url = {https://www.ncbi.nlm.nih.gov/pubmed/38423295},

doi = {10.1016/j.jaip.2024.02.021},

issn = {2213-2201 (Electronic)},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {J Allergy Clin Immunol Pract},

volume = {12},

number = {5},

pages = {1306-1312},

abstract = {BACKGROUND: Systemic mastocytosis (SM) is a clonal disorder of mast cells (MCs) frequently associated with vertebral osteoporosis (OP) and subsequent vertebral fractures (VFs). The natural history of this OP remains unclear. Importantly, we do not know whether OP represents an early event triggered alongside MC abnormalities, and whether MC clonality is sufficient to trigger osteoporosis. OBJECTIVE: To describe OP in patients with medullar clonality in cutaneous mastocytosis (CM) and monoclonal mast cell activation syndrome (MMAS) and to compare their osteoporosis characteristics with those of nonadvanced SM patients (bone marrow mastocytosis and indolent systemic mastocytosis). METHODS: We retrospectively analyzed clinical, biological, and densitometric data of 27 CM, 13 MMAS, and 135 SM patients from the Mastocytosis Expert Center (CEREMAST) in Toulouse, France. RESULTS: The OP (respectively 3.7, 30.8, and 34.1%) and VFs (0.0%, 15.4%, and 20%) were less frequent in CM than in MMAS and SM, despite the presence of clonal MCs in the bone marrow. Most patients with OP and VFs in the non-SM groups had the usual risk factors for OP. Interestingly, the only non-SM patient with a typical SM-like OP had high bone marrow tryptase, developed bone marrow KIT mutation during follow-up, and had a family history of SM. Our data show that OP is not a common clinical finding in CM but is frequent in MMAS. When OP and VFs occur in CM and MMAS patients, they differ from the usual phenotype of SM bone fragility. CONCLUSIONS: Our findings suggest that, in most CM patients, the meaning and management of OP differs from that of OP in MMAS and nonadvanced SM. Prospective longitudinal studies and the validation of predictors are needed to identify CM and MMAS patients developing SM-related OP.},

note = {Degboe, Yannick 

Severino-Freire, Maella 

Couture, Guillaume 

Apoil, Pol-Andre 

Gaudenzio, Nicolas 

Hermine, Olivier 

Ruyssen-Witrand, Adeline 

Paul, Carle 

Laroche, Michel 

Constantin, Arnaud 

Livideanu, Cristina Bulai 

eng 

Research Support, Non-U.S. Gov't 

2024/03/01 

J Allergy Clin Immunol Pract. 2024 May;12(5):1306-1312. doi: 10.1016/j.jaip.2024.02.021. Epub 2024 Feb 27.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN2123,

title = {Diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease: Data from the French Tw-IRD registry},

author = {D. Caillet Portillo and X. Puechal and M. Masson and M. Kostine and A. Michaut and A. Ramon and D. Wendling and N. Costedoat-Chalumeau and P. Richette and H. Marotte and J. Vix-Portet and J. J. Dubost and S. Ottaviani and G. Mouterde and A. Grasland and A. Frazier and V. Germain and F. Coury and A. Tournadre and M. Soubrier and L. Cavalie and P. Brevet and L. Zabraniecki and B. Jamard and G. Couture and L. Arnaud and C. Richez and Y. Degboe and A. Ruyssen-Witrand and A. Constantin},

url = {https://www.ncbi.nlm.nih.gov/pubmed/38141787},

doi = {10.1016/j.jinf.2023.12.010},

issn = {1532-2742 (Electronic) 0163-4453 (Linking)},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {J Infect},

volume = {88},

number = {2},

pages = {132-138},

abstract = {OBJECTIVES: Tropheryma whipplei infection can manifest as inflammatory joint symptoms, which can lead to misdiagnosis of inflammatory rheumatic disease and the use of disease-modifying antirheumatic drugs. We investigated the impact of diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease. METHODS: We initiated a registry including patients with disease-modifying antirheumatic drugs-treated inflammatory rheumatic disease who were subsequently diagnosed with Tropheryma whipplei infection. We collected clinical, biological, treatment data of the inflammatory rheumatic disease, of Tropheryma whipplei infection, and impact of antibiotics on the evolution of inflammatory rheumatic disease. RESULTS: Among 73 inflammatory rheumatic disease patients, disease-modifying antirheumatic drugs initiation triggered extra-articular manifestations in 27% and resulted in stabilisation (51%), worsening (34%), or improvement (15%) of inflammatory rheumatic disease. At the diagnosis of Tropheryma whipplei infection, all patients had rheumatological symptoms (mean age 58 years, median inflammatory rheumatic disease duration 79 months), 84% had extra-rheumatological manifestations, 93% had elevated C-reactive protein, and 86% had hypoalbuminemia. Treatment of Tropheryma whipplei infection consisted mainly of doxycycline plus hydroxychloroquine, leading to remission of Tropheryma whipplei infection in 79% of cases. Antibiotic treatment of Tropheryma whipplei infection was associated with remission of inflammatory rheumatic disease in 93% of cases and enabled disease-modifying antirheumatic drugs and glucocorticoid discontinuation in most cases. CONCLUSIONS: Tropheryma whipplei infection should be considered in inflammatory rheumatic disease patients with extra-articular manifestations, elevated C-reactive protein, and/or hypoalbuminemia before disease-modifying antirheumatic drugs initiation or in inflammatory rheumatic disease patients with an inadequate response to one or more disease-modifying antirheumatic drugs. Positive results of screening and diagnostic tests for Tropheryma whipplei infection involve antibiotic treatment, which is associated with complete recovery of Tropheryma whipplei infection and rapid remission of inflammatory rheumatic disease, allowing disease-modifying antirheumatic drugs and glucocorticoid discontinuation.},

note = {Caillet Portillo, Damien 

Puechal, Xavier 

Masson, Maeva 

Kostine, Marie 

Michaut, Alexia 

Ramon, Andre 

Wendling, Daniel 

Costedoat-Chalumeau, Nathalie 

Richette, Pascal 

Marotte, Hubert 

Vix-Portet, Justine 

Dubost, Jean-Jacques 

Ottaviani, Sebastien 

Mouterde, Gael 

Grasland, Anne 

Frazier, Aline 

Germain, Vincent 

Coury, Fabienne 

Tournadre, Anne 

Soubrier, Martin 

Cavalie, Laurent 

Brevet, Pauline 

Zabraniecki, Laurent 

Jamard, Benedicte 

Couture, Guillaume 

Arnaud, Laurent 

Richez, Christophe 

Degboe, Yannick 

Ruyssen-Witrand, Adeline 

Constantin, Arnaud 

eng 

England 

2023/12/24 

J Infect. 2024 Feb;88(2):132-138. doi: 10.1016/j.jinf.2023.12.010. Epub 2023 Dec 22.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Salles2024,

title = {Differential DNA methylation in iPSC-derived dopaminergic neurons: a step forward on the role of SNORD116 microdeletion in the pathophysiology of addictive behavior in Prader-Willi syndrome},

author = {Juliette Salles and Sanaa Eddiry and Saber Amri and Mélissa Galindo and Emmanuelle Lacassagne and Simon George and Xavier Mialhe and Émeline Lhuillier and Nicolas Franchitto and Freddy Jeanneteau and Isabelle Gennero and Jean Pierre Salles and Maithé Tauber},

doi = {10.1038/s41380-024-02542-4},

issn = {14765578},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {Molecular Psychiatry},

number = {March},

publisher = {Springer US},

abstract = {Introduction: A microdeletion including the SNORD116 gene (SNORD116 MD) has been shown to drive the Prader-Willi syndrome (PWS) features. PWS is a neurodevelopmental disorder clinically characterized by endocrine impairment, intellectual disability and psychiatric symptoms such as a lack of emotional regulation, impulsivity, and intense temper tantrums with outbursts. In addition, this syndrome is associated with a nutritional trajectory characterized by addiction-like behavior around food in adulthood. PWS is related to the genetic loss of expression of a minimal region that plays a potential role in epigenetic regulation. Nevertheless, the role of the SNORD116 MD in DNA methylation, as well as the impact of the oxytocin (OXT) on it, have never been investigated in human neurons. Methods: We studied the methylation marks in induced pluripotent stem-derived dopaminergic neurons carrying a SNORD116 MD in comparison with those from an age-matched adult healthy control. We also performed identical neuron differentiation in the presence of OXT. We performed a genome-wide DNA methylation analysis from the iPSC-derived dopaminergic neurons by reduced-representation bisulfite sequencing. In addition, we performed RNA sequencing analysis in these iPSC-derived dopaminergic neurons differentiated with or without OXT. Results: The analysis revealed that 153,826 cytosines were differentially methylated between SNORD116 MD neurons and control neurons. Among the differentially methylated genes, we determined a list of genes also differentially expressed. Enrichment analysis of this list encompassed the dopaminergic system with COMT and SLC6A3. COMT displayed hypermethylation and under-expression in SNORD116 MD, and SLC6A3 displayed hypomethylation and over-expression in SNORD116 MD. RT-qPCR confirmed significant over-expression of SLC6A3 in SNORD116 MD neurons. Moreover, the expression of this gene was significantly decreased in the case of OXT adjunction during the differentiation. Conclusion: SNORD116 MD dopaminergic neurons displayed differential methylation and expression in the COMT and SLC6A3 genes, which are related to dopaminergic clearance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lacouture_lfa-1_2024,

title = {LFA-1 nanoclusters integrate TCR stimulation strength to tune T-cell cytotoxic activity},

author = {Claire Lacouture and Beatriz Chaves and Delphine Guipouy and Raïssa Houmadi and Valérie Duplan-Eche and Sophie Allart and Nicolas Destainville and Loïc Dupré},

url = {https://www.nature.com/articles/s41467-024-44688-3},

doi = {10.1038/s41467-024-44688-3},

issn = {2041-1723},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {Nature Communications},

volume = {15},

number = {1},

pages = {407},

abstract = {T-cell cytotoxic function relies on the cooperation between the highly specific but poorly adhesive T-cell receptor (TCR) and the integrin LFA-1. How LFA-1-mediated adhesion may scale with TCR stimulation strength is ill-defined. Here, we show that LFA-1 conformation activation scales with TCR stimulation to calibrate human T-cell cytotoxicity. Super-resolution microscopy analysis reveals that >1000 LFA-1 nanoclusters provide a discretized platform at the immunological synapse to translate TCR engagement and density of the LFA-1 ligand ICAM-1 into graded adhesion. Indeed, the number of high-affinity conformation LFA-1 nanoclusters increases as a function of TCR triggering strength. Blockade of LFA-1 conformational activation impairs adhesion to target cells and killing. However, it occurs at a lower TCR stimulation threshold than lytic granule exocytosis implying that it licenses, rather than directly controls, the killing decision. We conclude that the organization of LFA-1 into nanoclusters provides a calibrated system to adjust T-cell killing to the antigen stimulation strength.},

note = {Number: 1 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Malnou2023,

title = {Editorial: Recent highlights in the development of therapeutic antiviral strategies},

author = {Cécile E. Malnou and Gaëtan Ligat},

doi = {10.3389/fmicb.2023.1338999},

issn = {1664-302X},

year  = {2023},

date = {2023-12-05},

urldate = {2023-12-05},

journal = {Front. Microbiol.},

volume = {14},

publisher = {Frontiers Media SA},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Scholaert2023,

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

author = {Manon Scholaert and Mathias Peries and Emilie Braun and Jeremy Martin and Nadine Serhan and Alexia Loste and Audrey Bruner and Lilian Basso and Benoit Chaput and Eric Merle and Pascal Descargues and Emeline Pages and Nicolas Gaudenzio},

url = {https://www.biorxiv.org/content/10.1101/2023.09.22.558940v1},

year  = {2023},

date = {2023-09-27},

journal = {bioRxiv},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37748654,

title = {Widespread monoclonal IgE antibody convergence to an immunodominant, proanaphylactic Ara h 2 epitope in peanut allergy},

author = {Derek Croote and Joyce J W Wong and Cyprien Pecalvel and Edouard Leveque and Natacha Casanovas and Jasper B J Kamphuis and Paige Creeks and Johanna Romero and Saba Sohail and Daniel Bedinger and Kari C Nadeau and Rebecca S Chinthrajah and Laurent L Reber and Henry B Lowman},

doi = {10.1016/j.jaci.2023.08.035},

issn = {1097-6825},

year  = {2023},

date = {2023-09-01},

urldate = {2023-09-01},

journal = {J Allergy Clin Immunol},

abstract = {BACKGROUND: Despite their central role in peanut allergy, human monoclonal IgE antibodies have eluded characterization.nnOBJECTIVE: We sought to define the sequences, affinities, clonality, and functional properties of human monoclonal IgE antibodies in peanut allergy.nnMETHODS: We applied our single-cell RNA sequencing-based SEQ SIFTER discovery platform to samples from allergic individuals who varied by age, sex, ethnicity, and geographic location in order to understand commonalities in the human IgE response to peanut allergens. Select antibodies were then recombinantly expressed and characterized for their allergen and epitope specificity, affinity, and functional properties.nnRESULTS: We found striking convergent evolution of IgE monoclonal antibodies (mAbs) from several clonal families comprising both memory B cells and plasmablasts. These antibodies bound with subnanomolar affinity to the immunodominant peanut allergen Ara h 2, specifically a linear, repetitive motif. Further characterization of these mAbs revealed their ability to single-handedly cause affinity-dependent degranulation of human mast cells and systemic anaphylaxis on peanut allergen challenge in humanized mice. Finally, we demonstrated that these mAbs, reengineered as IgGs, inhibit significant, but variable, amounts of Ara h 2- and peanut-mediated degranulation of mast cells sensitized with allergic plasma.nnCONCLUSIONS: Convergent evolution of IgE mAbs in peanut allergy is a common phenomenon that can reveal immunodominant epitopes on major allergenic proteins. Understanding the functional properties of these molecules is key to developing therapeutics, such as competitive IgG inhibitors, that are able to stoichiometrically outcompete endogenous IgE for allergen and thereby prevent allergic cascade in cases of accidental allergen exposure.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37697719,

title = {Single-cell RNA sequencing identifies senescence as therapeutic target in rhabdomyolysis-induced acute kidney injury},

author = {Snigdha N Rao and Margot Zahm and Audrey Casemayou and Marie Buleon and Stanislas Faguer and Guylène Feuillet and Jason S Iacovoni and Olivier P Joffre and Ignacio Gonzalez-Fuentes and Emeline Lhuillier and Frédéric Martins and Elodie Riant and Alexia Zakaroff-Girard and Joost P Schanstra and Jean Sébastien Saulnier Blache and Julie Belliere},

doi = {10.1093/ndt/gfad199},

issn = {1460-2385},

year  = {2023},

date = {2023-09-01},

urldate = {2023-09-01},

journal = {Nephrol Dial Transplant},

abstract = {BACKGROUND: The role of macrophages in the development of rhabdomyolysis induced acute kidney injury (RM-AKI) has been established, but an in-depth understanding of the changes in the immune landscape could help to improve targeted strategies. Whereas senescence is usually associated with chronic kidney processes, we also wished to explore whether senescence could also occur in AKI and whether senolytics could act on immune cells.nnMETHODS: Single-cell RNA sequencing was used in the murine glycerol-induced RM-AKI model to dissect the transcriptomic characteristics of CD45+ live cells sorted from kidneys 2 days after injury. Public datasets from murine AKI models were reanalyzed to explore cellular senescence signature in tubular epithelial cells (TECs). A combination of senolytics (dasatinib and quercetin, DQ) was administered to mice exposed or not to RM-AKI.nnRESULTS: Unsupervised clustering of nearly 17,000 single-cell transcriptomes identified 7 known immune cell clusters. Sub-clustering of the mononuclear phagocyte cells (MPC), revealed 9 distinct cell sub-populations differently modified with RM. One macrophage cluster was particularly interesting since it behaved as a critical node in a trajectory connecting one MCHIIhigh cluster only present in control to 2 MCHIIlow clusters only present in RM-AKI. This critical cluster expressed a senescence gene signature, that was very different from that of the TECs. Senolytic DQ treatment blocked the switch from a F4/80highCD11blow to F4/80lowCD11bhigh phenotype, which correlated with prolonged nephroprotection in RM-AKI.nnCONCLUSIONS: scRNASeq unmasked novel transitional macrophage subpopulation associated with RM-AKI characterized by the activation of cellular senescence processes. This work provides a proof-of-concept that senolytics nephroprotective effects may rely, at least in part, on subtle immune modulation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Martin2023,

title = {The Yin and the Yang of extracellular vesicles during viral infections},

author = {Charlène Martin and Gaëtan Ligat and Cécile E. Malnou},

doi = {10.1016/j.bj.2023.100659},

issn = {2319-4170},

year  = {2023},

date = {2023-09-00},

urldate = {2023-09-00},

journal = {Biomedical Journal},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Osma-Garcia2023b,

title = {The RNA binding proteins TIA1 and TIAL1 promote Mcl1 mRNA translation to protect germinal center responses from apoptosis},

author = {Osma-Garcia, Ines C. 

and Mouysset, Mailys 

and Capitan-Sobrino, Dunja 

and Aubert, Yann 

and Turner, Martin 

and Diaz-Mu{ñ}oz, Manuel D.},

url = {https://doi.org/10.1038/s41423-023-01063-4},

doi = {10.1038/s41423-023-01063-4},

issn = {2042-0226},

year  = {2023},

date = {2023-07-20},

urldate = {2023-07-20},

journal = {Cellular & Molecular Immunology},

abstract = {Germinal centers (GCs) are essential for the establishment of long-lasting antibody responses. GC B cells rely on post-transcriptional RNA mechanisms to translate activation-associated transcriptional programs into functional changes in the cell proteome. However, the critical proteins driving these key mechanisms are still unknown. Here, we show that the RNA binding proteins TIA1 and TIAL1 are required for the generation of long-lasting GC responses. TIA1- and TIAL1-deficient GC B cells fail to undergo antigen-mediated positive selection, expansion and differentiation into B-cell clones producing high-affinity antibodies. Mechanistically, TIA1 and TIAL1 control the transcriptional identity of dark- and light-zone GC B cells and enable timely expression of the prosurvival molecule MCL1. Thus, we demonstrate here that TIA1 and TIAL1 are key players in the post-transcriptional program that selects high-affinity antigen-specific GC B cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tauber#2023,

title = {Landscape of mast cell populations across organs in mice and humans},

author = {Marie Tauber# and Lilian Basso# and Jeremy Martin# and Luciana Bostan and Marlene Magalhaes Pinto and Guilhem R Thierry and Raïssa Houmadi and Nadine Serhan and Alexia Loste and Camille Blériot and Jasper B J Kamphuis and Mirjana Grujic and Lena Kjellén and Gunnar Pejler and Carle Paul and Xinzhong Dong and Stephen J Galli and Laurent L Reber and Florent Ginhoux and Marc Bajenoff and Rebecca Gentek and Nicolas Gaudenzio},

url = {https://pubmed.ncbi.nlm.nih.gov/37462672/},

doi = {10.1084},

year  = {2023},

date = {2023-07-18},

urldate = {2023-07-18},

journal = {Journal of Experimental Medicine},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37012202,

title = {C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress-Induced Ferroptosis in FLT3-Mutant Leukemia},

author = {Marie Sabatier and Rudy Birsen and Laura Lauture and Sarah Mouche and Paolo Angelino and Jonas Dehairs and Léa Goupille and Ismael Boussaid and Maël Heiblig and Emeline Boet and Ambrine Sahal and Estelle Saland and Juliana C Santos and Marc Armengol and Miranda Fernández-Serrano and Thomas Farge and Guillaume Cognet and Federico Simonetta and Corentin Pignon and Antoine Graffeuil and Céline Mazzotti and Hervé Avet-Loiseau and Océane Delos and Justine Bertrand-Michel and Amélie Chedru and Vilma Dembitz and Paolo Gallipoli and Natasha S Anstee and Sun Loo and Andrew H Wei and Martin Carroll and Armelle Goubard and Rémy Castellano and Yves Collette and François Vergez and Véronique Mansat-De Mas and Sarah Bertoli and Suzanne Tavitian and Muriel Picard and Christian Récher and Nathalie Bourges-Abella and Fanny Granat and Olivier Kosmider and Pierre Sujobert and Benoit Colsch and Carine Joffre and Lucille Stuani and Johannes V Swinnen and Hervé Guillou and Gael Roué and Nawad Hakim and Anne S Dejean and Petros Tsantoulis and Clément Larrue and Didier Bouscary and Jerome Tamburini and Jean-Emmanuel Sarry},

doi = {10.1158/2159-8290.CD-22-0411},

issn = {2159-8290},

year  = {2023},

date = {2023-07-01},

urldate = {2023-07-01},

journal = {Cancer Discov},

volume = {13},

number = {7},

pages = {1720--1747},

abstract = {Although transcription factor CCAAT-enhancer binding protein α (C/EBPα) is critical for normal and leukemic differentiation, its role in cell and metabolic homeostasis is largely unknown in cancer. Here, multiomics analyses uncovered a coordinated activation of C/EBPα and Fms-like tyrosine kinase 3 (FLT3) that increased lipid anabolism in vivo and in patients with FLT3-mutant acute myeloid leukemia (AML). Mechanistically, C/EBPα regulated the fatty acid synthase (FASN)-stearoyl-CoA desaturase (SCD) axis to promote fatty acid (FA) biosynthesis and desaturation. We further demonstrated that FLT3 or C/EBPα inactivation decreased monounsaturated FA incorporation to membrane phospholipids through SCD downregulation. Consequently, SCD inhibition enhanced susceptibility to lipid redox stress that was exploited by combining FLT3 and glutathione peroxidase 4 inhibition to trigger lipid oxidative stress, enhancing ferroptotic death of FLT3-mutant AML cells. Altogether, our study reveals a C/EBPα function in lipid homeostasis and adaptation to redox stress, and a previously unreported vulnerability of FLT3-mutant AML to ferroptosis with promising therapeutic application.nnSIGNIFICANCE: FLT3 mutations are found in 30% of AML cases and are actionable by tyrosine kinase inhibitors. Here, we discovered that C/EBPα regulates FA biosynthesis and protection from lipid redox stress downstream mutant-FLT3 signaling, which confers a vulnerability to ferroptosis upon FLT3 inhibition with therapeutic potential in AML. This article is highlighted in the In This Issue feature, p. 1501.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37080596,

title = {Effects of a Small-Molecule Perforin Inhibitor in a Mouse Model of CD8 T Cell-Mediated Neuroinflammation},

author = {Carmen Gonzalez-Fierro and Coralie Fonte and Eloïse Dufourd and Vincent Cazaentre and Sidar Aydin and Britta Engelhardt and Rachel R Caspi and Biying Xu and Guillaume Martin-Blondel and Julie A Spicer and Joseph A Trapani and Jan Bauer and Roland S Liblau and Chloé Bost},

doi = {10.1212/NXI.0000000000200117},

issn = {2332-7812},

year  = {2023},

date = {2023-07-01},

urldate = {2023-07-01},

journal = {Neurol Neuroimmunol Neuroinflamm},

volume = {10},

number = {4},

abstract = {BACKGROUND AND OBJECTIVES: Alteration of the blood-brain barrier (BBB) at the interface between blood and CNS parenchyma is prominent in most neuroinflammatory diseases. In several neurologic diseases, including cerebral malaria and Susac syndrome, a CD8 T cell-mediated targeting of endothelial cells of the BBB (BBB-ECs) has been implicated in pathogenesis.nnMETHODS: In this study, we used an experimental mouse model to evaluate the ability of a small-molecule perforin inhibitor to prevent neuroinflammation resulting from cytotoxic CD8 T cell-mediated damage of BBB-ECs.nnRESULTS: Using an in vitro coculture system, we first identified perforin as an essential molecule for killing of BBB-ECs by CD8 T cells. We then found that short-term pharmacologic inhibition of perforin commencing after disease onset restored motor function and inhibited the neuropathology. Perforin inhibition resulted in preserved BBB-EC viability, maintenance of the BBB, and reduced CD8 T-cell accumulation in the brain and retina.nnDISCUSSION: Therefore, perforin-dependent cytotoxicity plays a key role in the death of BBB-ECs inflicted by autoreactive CD8 T cells in a preclinical model and potentially represents a therapeutic target for CD8 T cell-mediated neuroinflammatory diseases, such as cerebral malaria and Susac syndrome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37236806,

title = {Immunohistologic Features of Cerebral Venous Thrombosis Due to Vaccine-Induced Immune Thrombotic Thrombocytopenia},

author = {Thomas Geeraerts and Céline Guilbeau-Frugier and Cédric Garcia and Vincent Memier and Nicolas Raposo and Fabrice Bonneville and Céline Gales and Jean Darcourt and Sophie Voisin and Agnès Ribes and Marie Piel-Julian and Fanny Bounes and Jean François Albucher and Franck-Emmanuel Roux and Jacques Izopet and Norbert Telmon and Jean Marc Olivot and Pierre Sié and Jan Bauer and Bernard Payrastre and Roland S Liblau},

doi = {10.1212/NXI.0000000000200127},

issn = {2332-7812},

year  = {2023},

date = {2023-07-01},

urldate = {2023-07-01},

journal = {Neurol Neuroimmunol Neuroinflamm},

volume = {10},

number = {4},

abstract = {OBJECTIVES: Vaccine-induced immune thrombotic thrombocytopenia (VITT), a recently described entity characterized by thrombosis at unusual locations such as cerebral venous sinus and splanchnic vein, has been rarely described after adenoviral-encoded COVID-19 vaccines. In this study, we report the immunohistological correlates in 3 fatal cases of cerebral venous thrombosis related to VITT analyzed at an academic medical center.nnMETHODS: Detailed neuropathologic studies were performed in 3 cases of cerebral venous thrombosis related to VITT after adenoviral COVID-19 vaccination.nnRESULTS: Autopsy revealed extensive cerebral vein thrombosis in all 3 cases. Polarized thrombi were observed with a high density of neutrophils in the core and a low density in the tail. Endothelial cells adjacent to the thrombus were largely destroyed. Markers of neutrophil extracellular trap and complement activation were present at the border and within the cerebral vein thrombi. SARS-CoV-2 spike protein was detected within the thrombus and in the adjacent vessel wall.nnDISCUSSION: Data indicate that neutrophils and complement activation associated with antispike immunity triggered by the vaccine is probably involved in the disease process.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37400646,

title = {The immunopathogenesis of narcolepsy type 1},

author = {Roland S Liblau and Daniela Latorre and Birgitte R Kornum and Yves Dauvilliers and Emmanuel J Mignot},

doi = {10.1038/s41577-023-00902-9},

issn = {1474-1741},

year  = {2023},

date = {2023-07-01},

urldate = {2023-07-01},

journal = {Nat Rev Immunol},

abstract = {Narcolepsy type 1 (NT1) is a chronic sleep disorder resulting from the loss of a small population of hypothalamic neurons that produce wake-promoting hypocretin (HCRT; also known as orexin) peptides. An immune-mediated pathology for NT1 has long been suspected given its exceptionally tight association with the MHC class II allele HLA-DQB1*06:02, as well as recent genetic evidence showing associations with polymorphisms of T cell receptor genes and other immune-relevant loci and the increased incidence of NT1 that has been observed after vaccination with the influenza vaccine Pandemrix. The search for both self-antigens and foreign antigens recognized by the pathogenic T cell response in NT1 is ongoing. Increased T cell reactivity against HCRT has been consistently reported in patients with NT1, but data demonstrating a primary role for T cells in neuronal destruction are currently lacking. Animal models are providing clues regarding the roles of autoreactive CD4 and CD8 T cells in the disease. Elucidation of the pathogenesis of NT1 will allow for the development of targeted immunotherapies at disease onset and could serve as a model for other immune-mediated neurological diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pichler2023b,

title = {TCR-independent CD137 (4-1BB) signaling promotes CD8+-exhausted T cell proliferation and terminal differentiation},

author = {Andrea C. Pichler and Nadège Carrié and Marine Cuisinier and Samira Ghazali and Allison Voisin and Pierre-Paul Axisa and Marie Tosolini and Céline Mazzotti and Dominic P. Golec and Sabrina Maheo and Laura do Souto and Rüçhan Ekren and Eve Blanquart and Lea Lemaitre and Virginie Feliu and Marie-Véronique Joubert and Jennifer L. Cannons and Camille Guillerey and Hervé Avet-Loiseau and Tania H. Watts and Benoit L. Salomon and Olivier Joffre and Yenkel Grinberg-Bleyer and Pamela L. Schwartzberg and Liliana E. Lucca and Ludovic Martinet},

doi = {10.1016/j.immuni.2023.06.007},

issn = {1074-7613},

year  = {2023},

date = {2023-07-00},

journal = {Immunity},

volume = {56},

number = {7},

pages = {1631--1648.e10},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Scholaert†2023,

title = {3D deconvolution of human skin immune architecture with Multiplex Annotated Tissue Imaging System},

author = {Manon Scholaert† and Raissa Houmadi† and Jeremy Martin† and Nadine Serhan† and Marie Tauber and Emilie Braun and Lilian Basso and Eric Merle and Pascal Descargues and Manuelle Viguier and Cécile Lesort and Benoît Chaput and Jean Kanitakis and Denis Jullien and Cristina Bulai Livideanu and Laurence Lamant and Emeline Pagès and Nicolas Gaudenzio},

url = {https://www-science-org.proxy.insermbiblio.inist.fr/doi/10.1126/sciadv.adf9491},

doi = {10.1126/sciadv.adf9491},

year  = {2023},

date = {2023-06-07},

journal = {Science Advances},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{block_systemic_2023,

title = {Systemic Inflammation and Normocytic Anemia in DOCK11 Deficiency},

author = {Block, Jana and Rashkova, Christina and Castanon, Irinka and Zoghi, Samaneh and Platon, Jessica and Ardy, Rico C. and Fujiwara, Mitsuhiro and Chaves, Beatriz and Schoppmeyer, Rouven and van der Made, Caspar I. and Jimenez Heredia, Raul and Harms, Frederike L. and Alavi, Samin and Alsina, Laia and Sanchez Moreno, Paula and Ávila Polo, Rainiero and Cabrera-Pérez, Rocío and Kostel Bal, Sevgi and Pfajfer, Laurène and Ransmayr, Bernhard and Mautner, Anna-Katharina and Kondo, Ryohei and Tinnacher, Anna and Caldera, Michael and Schuster, Michael and Domínguez Conde, Cecilia and Platzer, René and Salzer, Elisabeth and Boyer, Thomas and Brunner, Han G. and Nooitgedagt-Frons, Judith E. and Iglesias, Estíbaliz and Deyà-Martinez, Angela and Camacho-Lovillo, Marisol and Menche, Jörg and Bock, Christoph and Huppa, Johannes B. and Pickl, Winfried F. and Distel, Martin and Yoder, Jeffrey A. and Traver, David and Engelhardt, Karin R. and Linden, Tobias and Kager, Leo and Hannich, J. Thomas and Hoischen, Alexander and Hambleton, Sophie and Illsinger, Sabine and Da Costa, Lydie and Kutsche, Kerstin and Chavoshzadeh, Zahra and van Buul, Jaap D. and Antón, Jordi and Calzada-Hernández, Joan and Neth, Olaf and Viaud, Julien and Nishikimi, Akihiko and Dupré, Loïc and Boztug, Kaan},

doi = {10.1056/NEJMoa2210054},

issn = {1533-4406},

year  = {2023},

date = {2023-06-01},

journal = {N Engl J Med},

abstract = {BACKGROUND: Increasing evidence links genetic defects affecting actin-regulatory proteins to diseases with severe autoimmunity and autoinflammation, yet the underlying molecular mechanisms are poorly understood. Dedicator of cytokinesis 11 (DOCK11) activates the small Rho guanosine triphosphatase (GTPase) cell division cycle 42 (CDC42), a central regulator of actin cytoskeleton dynamics. The role of DOCK11 in human immune-cell function and disease remains unknown. 

METHODS: We conducted genetic, immunologic, and molecular assays in four patients from four unrelated families who presented with infections, early-onset severe immune dysregulation, normocytic anemia of variable severity associated with anisopoikilocytosis, and developmental delay. Functional assays were performed in patient-derived cells, as well as in mouse and zebrafish models. 

RESULTS: We identified rare, X-linked germline mutations in DOCK11 in the patients, leading to a loss of protein expression in two patients and impaired CDC42 activation in all four patients. Patient-derived T cells did not form filopodia and showed abnormal migration. In addition, the patient-derived T cells, as well as the T cells from Dock11-knockout mice, showed overt activation and production of proinflammatory cytokines that were associated with an increased degree of nuclear translocation of nuclear factor of activated T cell 1 (NFATc1). Anemia and aberrant erythrocyte morphologic features were recapitulated in a newly generated dock11-knockout zebrafish model, and anemia was amenable to rescue on ectopic expression of constitutively active CDC42. 

CONCLUSIONS: Germline hemizygous loss-of-function mutations affecting the actin regulator DOCK11 were shown to cause a previously unknown inborn error of hematopoiesis and immunity characterized by severe immune dysregulation and systemic inflammation, recurrent infections, and anemia. (Funded by the European Research Council and others.).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}