Cargando…

Apoptosis in response to microbial infection induces autoreactive T(H)17 cells

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 elici...

Descripción completa

Detalles Bibliográficos
Autores principales: Campisi, Laura, Barbet, Gaetan, Ding, Yi, Esplugues, Enric, Flavell, Richard A., Blander, J. Magarian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079524/
https://www.ncbi.nlm.nih.gov/pubmed/27455420
http://dx.doi.org/10.1038/ni.3512
_version_ 1782462560251936768
author Campisi, Laura
Barbet, Gaetan
Ding, Yi
Esplugues, Enric
Flavell, Richard A.
Blander, J. Magarian
author_facet Campisi, Laura
Barbet, Gaetan
Ding, Yi
Esplugues, Enric
Flavell, Richard A.
Blander, J. Magarian
author_sort Campisi, Laura
collection PubMed
description 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 immune-stimulatory 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 T(H)17 subset of helper T cells, prominently associated with autoimmune disease. Once induced, the self-reactive T(H)17 cells promoted auto-inflammation and autoantibody generation. Our findings have implications for how infections precipitate autoimmunity.
format Online
Article
Text
id pubmed-5079524
institution National Center for Biotechnology Information
language English
publishDate 2016
record_format MEDLINE/PubMed
spelling pubmed-50795242017-01-25 Apoptosis in response to microbial infection induces autoreactive T(H)17 cells Campisi, Laura Barbet, Gaetan Ding, Yi Esplugues, Enric Flavell, Richard A. Blander, J. Magarian Nat Immunol Article 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 immune-stimulatory 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 T(H)17 subset of helper T cells, prominently associated with autoimmune disease. Once induced, the self-reactive T(H)17 cells promoted auto-inflammation and autoantibody generation. Our findings have implications for how infections precipitate autoimmunity. 2016-07-25 2016-09 /pmc/articles/PMC5079524/ /pubmed/27455420 http://dx.doi.org/10.1038/ni.3512 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Campisi, Laura
Barbet, Gaetan
Ding, Yi
Esplugues, Enric
Flavell, Richard A.
Blander, J. Magarian
Apoptosis in response to microbial infection induces autoreactive T(H)17 cells
title Apoptosis in response to microbial infection induces autoreactive T(H)17 cells
title_full Apoptosis in response to microbial infection induces autoreactive T(H)17 cells
title_fullStr Apoptosis in response to microbial infection induces autoreactive T(H)17 cells
title_full_unstemmed Apoptosis in response to microbial infection induces autoreactive T(H)17 cells
title_short Apoptosis in response to microbial infection induces autoreactive T(H)17 cells
title_sort apoptosis in response to microbial infection induces autoreactive t(h)17 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079524/
https://www.ncbi.nlm.nih.gov/pubmed/27455420
http://dx.doi.org/10.1038/ni.3512
work_keys_str_mv AT campisilaura apoptosisinresponsetomicrobialinfectioninducesautoreactiveth17cells
AT barbetgaetan apoptosisinresponsetomicrobialinfectioninducesautoreactiveth17cells
AT dingyi apoptosisinresponsetomicrobialinfectioninducesautoreactiveth17cells
AT espluguesenric apoptosisinresponsetomicrobialinfectioninducesautoreactiveth17cells
AT flavellricharda apoptosisinresponsetomicrobialinfectioninducesautoreactiveth17cells
AT blanderjmagarian apoptosisinresponsetomicrobialinfectioninducesautoreactiveth17cells