Interleukin-10 from CD4 + follicular regulatory T cells promotes the germinal center response

Sci Immunol. 2017 Oct 20;2(16):eaan4767. doi: 10.1126/sciimmunol.aan4767.

Abstract

CD4+ follicular regulatory T (Tfr) cells suppress B cell responses through modulation of follicular helper T (Tfh) cells and germinal center (GC) development. We found that Tfr cells can also promote the GC response through provision of interleukin-10 (IL-10) after acute infection with lymphocytic choriomeningitis virus (LCMV). Sensing of IL-10 by B cells was necessary for optimal development of the GC response. GC B cells formed in the absence of Treg cell-derived IL-10 displayed an altered dark zone state and decreased expression of the transcription factor Forkhead box protein 1 (FOXO1). IL-10 promoted nuclear translocation of FOXO1 in activated B cells. These data indicate that Tfr cells play a multifaceted role in the fine-tuning of the GC response and identify IL-10 as an important mediator by which Tfr cells support the GC reaction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arenaviridae Infections / immunology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / physiology
  • Cell Differentiation
  • Forkhead Box Protein O1 / genetics
  • Forkhead Box Protein O1 / metabolism
  • Germinal Center / immunology*
  • Germinal Center / physiology
  • Interleukin-10 / immunology*
  • Interleukin-10 / metabolism
  • Lymphocyte Activation
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Sequence Analysis, RNA
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / physiology

Substances

  • Forkhead Box Protein O1
  • Foxo1 protein, mouse
  • IL10 protein, human
  • IL10 protein, mouse
  • Interleukin-10