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

Caroline Stienne, Richard Virgen-Slane, Lisa Elmén, Marisol Veny, Sarah Huang, Jennifer Nguyen, Elizabeth Chappell, Mary Olivia Balmert, Jr Wen Shui, Michelle A. Hurchla, Mitchell Kronenberg, Scott N. Peterson, Kenneth M. Murphy, Carl F. Ware, John R. Šedý

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number110553
JournalCell Reports
Volume38
Issue number12
DOIs
StatePublished - Mar 22 2022

Keywords

  • B cell
  • CP: Immunology
  • CP: Microbiology
  • IgA
  • Tfh
  • Tfr
  • Treg
  • autoimmunity
  • germinal center
  • inhibitory receptor
  • microbiome

Fingerprint

Dive into the research topics of 'Btla signaling in conventional and regulatory lymphocytes coordinately tempers humoral immunity in the intestinal mucosa'. Together they form a unique fingerprint.

Cite this