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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
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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 |
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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 |
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