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Publication : Btla signaling in conventional and regulatory lymphocytes coordinately tempers humoral immunity in the intestinal mucosa.

First Author  Stienne C Year  2022
Journal  Cell Rep Volume  38
Issue  12 Pages  110553
PubMed ID  35320716 Mgi Jnum  J:324910
Mgi Id  MGI:7281993 Doi  10.1016/j.celrep.2022.110553
Citation  Stienne C, et al. (2022) Btla signaling in conventional and regulatory lymphocytes coordinately tempers humoral immunity in the intestinal mucosa. Cell Rep 38(12):110553
abstractText  The Btla inhibitory receptor limits innate and adaptive immune responses, both preventing the development of autoimmune disease and restraining anti-viral and anti-tumor responses. It remains unclear how the functions of Btla in diverse lymphocytes contribute to immunoregulation. Here, we show that Btla inhibits activation of genes regulating metabolism and cytokine signaling, including Il6 and Hif1a, indicating a regulatory role in humoral immunity. Within mucosal Peyer's patches, we find T-cell-expressed Btla-regulated Tfh cells, while Btla in T or B cells regulates GC B cell numbers. Treg-expressed Btla is required for cell-intrinsic Treg homeostasis that subsequently controls GC B cells. Loss of Btla in lymphocytes results in increased IgA bound to intestinal bacteria, correlating with altered microbial homeostasis and elevations in commensal and pathogenic bacteria. Together our studies provide important insights into how Btla functions as a checkpoint in diverse conventional and regulatory lymphocyte subsets to influence systemic immune responses.
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