Publications by authors named "Jonathan Charaix"

Thymically-derived Foxp3 regulatory T cells (T) critically control immunological tolerance. These cells are generated in the medulla through high affinity interactions with medullary thymic epithelial cells (mTEC) expressing the Autoimmune regulator (Aire). Recent advances have revealed that thymic T contain not only developing but also recirculating cells from the periphery.

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The transcription factor STAT1 plays a critical role in modulating the differentiation of CD4+ T cells producing IL-17 and GM-CSF, which promote the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). The protective role of STAT1 in MS and EAE has been largely attributed to its ability to limit pathogenic Th cells and promote Tregs. Using mice with selective deletion of STAT1 in T cells (STAT1CD4-Cre), we identified a potentially novel mechanism by which STAT1 regulates neuroinflammation independently of Foxp3+ Tregs.

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Interactions of developing T cells with Aire medullary thymic epithelial cells expressing high levels of MHCII molecules (mTEC) are critical for the induction of central tolerance in the thymus. In turn, thymocytes regulate the cellularity of Aire mTEC. However, it remains unknown whether thymocytes control the precursors of Aire mTEC that are contained in mTEC cells or other mTEC subsets that have recently been delineated by single-cell transcriptomic analyses.

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Systemic lupus erythematosus (SLE) patients have increased prevalence of metabolic syndrome but the underlying mechanisms are unknown. Toll-like receptor 7 (TLR7) that detects single stranded-RNA plays a key role in antimicrobial host defense and also contributes to the initiation and progression of SLE both in mice and humans. Here, we report the implication of TLR7 signaling in high fat diet (HFD)-induced metabolic syndrome and exacerbation of lupus autoimmunity in TLR8-deficient (TLR8ko) mice, which develop spontaneous lupus-like disease due to increased TLR7 signaling by dendritic cells (DCs).

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Medullary thymic epithelial cells (mTEC) purge the T cell repertoire of autoreactive thymocytes. Although dendritic cells (DC) reinforce this process by transporting innocuous peripheral self-antigens, the mechanisms that control their thymic entry remain unclear. Here we show that mTEC-CD4 thymocyte crosstalk regulates the thymus homing of SHPS-1 conventional DCs (cDC), plasmacytoid DCs (pDC) and macrophages.

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