Format

Send to

Choose Destination
Nat Immunol. 2016 Sep;17(9):1084-92. doi: 10.1038/ni.3512. Epub 2016 Jul 25.

Apoptosis in response to microbial infection induces autoreactive TH17 cells.

Author information

1
Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
2
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
3
Department of Pathology, New York University Langone Medical Center, New York, New York, USA.
4
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
5
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
6
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

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.

PMID:
27455420
PMCID:
PMC5079524
DOI:
10.1038/ni.3512
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center