Apoptosis in response to microbial infection induces autoreactive T H17 cells Academic Article uri icon

Overview

MeSH Major

  • Apoptosis
  • Autoantigens
  • Autoimmune Diseases
  • Citrobacter rodentium
  • Enterobacteriaceae Infections
  • Th17 Cells

abstract

  • Microbial infections often precede the onset of autoimmunity. How infections trigger autoimmunity remains poorly understood. We investigated the possibility that infection might create conditions that allow the stimulatory presentation of self peptides themselves and that this might suffice to elicit autoreactive T cell responses that lead to autoimmunity. Self-reactive CD4(+) T cells are major drivers of autoimmune disease, but their activation is normally prevented through regulatory mechanisms that limit the immunostimulatory presentation of self antigens. Here we found that the apoptosis of infected host cells enabled the presentation of self antigens by major histocompatibility complex class II molecules in an inflammatory context. This was sufficient for the generation of an autoreactive TH17 subset of helper T cells, prominently associated with autoimmune disease. Once induced, the self-reactive TH17 cells promoted auto-inflammation and autoantibody generation. Our findings have implications for how infections precipitate autoimmunity.

publication date

  • August 19, 2016

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5079524

Digital Object Identifier (DOI)

  • 10.1038/ni.3512

PubMed ID

  • 27455420

Additional Document Info

start page

  • 1084

end page

  • 92

volume

  • 17

number

  • 9