Role of SFB in autoimmune arthritis: an example of regulation of autoreactive T cell sensitivity in the gut

Gut Microbes. 2014 Mar-Apr;5(2):259-64. doi: 10.4161/gmic.28134. Epub 2014 Feb 6.

Abstract

A key role for segmented filamentous bacteria (SFB) has recently been demonstrated in several mouse models of autoimmune diseases, including autoimmune arthritis and multiple sclerosis. The mechanism governing the activation of systemic autoreactive T cell responses by such commensals in the gut, however, remained elusive. In this addendum, we discuss recent results addressing the local regulation of autoreactive T cell sensitivity by these unique bacteria. We found that the presence of SFB in the gut microbiota was sufficient to promote a local inflammatory microenvironment altering the T cell-intrinsic desensitization process normally occurring in response to chronic self-antigen stimulation. In the absence of this key tolerance checkpoint, sustained chronic T cell proliferation, IFNγ production, and B cell activation eventually led to the development of enhanced pathologies in a Th1-driven T cell-transfer model of autoimmune arthritis.

Keywords: T cell tuning; autoreactive T cells; commensal flora; gut; rheumatoid arthritis; segmented filamentous bacteria.

Publication types

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

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / immunology*
  • Bacteria / immunology
  • Gastrointestinal Tract / microbiology*
  • Mice
  • T-Lymphocytes / immunology*