The latest study from the Jill Roberts Institute, "A Cellular Tango: Immune and Nerve Cells Work Together to Fight Gut Infections," was published on September 6 in Nature. To read more, click here.     Dr. Gregory Sonnenberg wins inaugural award from the Society for Mucosal Immunology. To read more, click here.        

The Jill Roberts Institute for Research in Inflammatory Bowel Disease

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Apoptosis in response to microbial infection induces autoreactive TH17 cells.

TitleApoptosis in response to microbial infection induces autoreactive TH17 cells.
Publication TypeJournal Article
Year of Publication2016
AuthorsCampisi, L, Barbet, G, Ding, Y, Esplugues, E, Flavell, RA, J Blander, M
JournalNat Immunol
Volume17
Issue9
Pagination1084-92
Date Published2016 Sep
ISSN1529-2916
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.

DOI10.1038/ni.3512
Alternate JournalNat. Immunol.
PubMed ID27455420
PubMed Central IDPMC5079524
Grant ListP01 DK072201 / DK / NIDDK NIH HHS / United States
R01 AI073899 / AI / NIAID NIH HHS / United States
R01 AI095245 / AI / NIAID NIH HHS / United States
R21 AI080959 / AI / NIAID NIH HHS / United States
R56 AI073899 / AI / NIAID NIH HHS / United States