@article{43763515c92d4fb58ad388458e7035be,
title = "Apoptosis in response to microbial infection induces autoreactive T H17 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.",
author = "Laura Campisi and Gaetan Barbet and Yi Ding and Enric Esplugues and Flavell, {Richard A.} and Blander, {J. Magarian}",
note = "Funding Information: We thank S. Lira, G. Furtado, H. Xiong, G. Yeretssian, M.K. Jenkins and members of the Blander laboratory for discussions; D. Amsen and R.J. Cummings for critical reading of the manuscript; A. Rialdi for help with statistical analyses; J. Ochando and C. Bare for flow cytometry; A. Soto and M.J. Suarez (the NIH Tetramer Core Facility at Emory University) for I-AbOVA(328-337) and control tetramers; H. Xiong (The Icahn School of Medicine at Mount Sinai) for LM-OVA bacteria; A. Morelli (University of Pittsburgh) for 1H3.1 mice; B. Finlay and M. Croxen (University of British Columbia) for wild-type and ΔEspF C. rodentium and plasmid pMAC5; H.P. Schweizer (Colorado State University) for plasmid pTNS2; D. Mazel (Institut Pasteur) for MFDpir bacteria; and I. Marazzi, V. Verhasselt, S.E.F. Campisi, G.C. Chiesa, Jr., M.A. Blander, S.J. Blander and the late L. Mayer for advice and support. Supported by the National Institute of Diabetes and Digestive and Kidney Diseases (DK072201 to J.M.B.), the National Institute of Allergy and Infectious Diseases (AI073899, AI080959 and AI095245 to J.M.B.), the Arthritis Foundation (L.C.), the Crohn's and Colitis Foundation of America (G.B.), the Burroughs Wellcome Fund (J.M.B.), the Irma Hirschl and Monique Weill-Caulier Charitable Trust Funds (J.M.B.), the American Cancer Society (J.M.B.) and the Leukemia and Lymphoma Society (J.M.B.). Publisher Copyright: {\textcopyright} 2016 Nature America, Inc.",
year = "2016",
month = aug,
day = "19",
doi = "10.1038/ni.3512",
language = "English",
volume = "17",
pages = "1084--1092",
journal = "Nature immunology",
issn = "1529-2908",
number = "9",
}