title: Apoptosis in response to microbial infection induces autoreactive 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.
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Campisi
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Gaetan
authors.initials: G
authors.lastname: Barbet
authors.affiliation: Department of Pathology, New York University Langone Medical Center, New York, New York, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Enric
authors.initials: E
authors.lastname: Esplugues
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: J Magarian
authors.identifier: 0000-0001-9207-1700
authors.initials: JM
authors.lastname: Blander
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D017209:Apoptosis; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D015551:Autoimmunity; D044082:Citrobacter rodentium / Q000276:immunology*; D004756:Enterobacteriaceae Infections / Q000150:complications / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011828:Radiation Chimera; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D016753:Interleukin-10