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Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice
Both animal model and human studies indicate that commensal bacteria may modify type 1 diabetes (T1D) development. However, the underlying mechanisms by which gut microbes could trigger or protect from diabetes are not fully understood, especially the interaction of commensal bacteria with pathogeni...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030808/ https://www.ncbi.nlm.nih.gov/pubmed/27621416 http://dx.doi.org/10.1084/jem.20160526 |
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author | Tai, Ningwen Peng, Jian Liu, Fuqiang Gulden, Elke Hu, Youjia Zhang, Xiaojun Chen, Li Wong, F. Susan Wen, Li |
author_facet | Tai, Ningwen Peng, Jian Liu, Fuqiang Gulden, Elke Hu, Youjia Zhang, Xiaojun Chen, Li Wong, F. Susan Wen, Li |
author_sort | Tai, Ningwen |
collection | PubMed |
description | Both animal model and human studies indicate that commensal bacteria may modify type 1 diabetes (T1D) development. However, the underlying mechanisms by which gut microbes could trigger or protect from diabetes are not fully understood, especially the interaction of commensal bacteria with pathogenic CD8 T cells. In this study, using islet-specific glucose-6-phosphatase catalytic subunit–related protein (IGRP)–reactive CD8 T cell receptor NY8.3 transgenic nonobese diabetic mice, we demonstrated that MyD88 strongly modulates CD8(+) T cell–mediated T1D development via the gut microbiota. Some microbial protein peptides share significant homology with IGRP. Both the microbial peptide mimic of Fusobacteria and the bacteria directly activate IGRP-specific NY8.3 T cells and promote diabetes development. Thus, we provide evidence of molecular mimicry between microbial antigens and an islet autoantigen and a novel mechanism by which the diabetogenicity of CD8(+) T cells can be regulated by innate immunity and the gut microbiota. |
format | Online Article Text |
id | pubmed-5030808 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-50308082017-03-19 Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice Tai, Ningwen Peng, Jian Liu, Fuqiang Gulden, Elke Hu, Youjia Zhang, Xiaojun Chen, Li Wong, F. Susan Wen, Li J Exp Med Research Articles Both animal model and human studies indicate that commensal bacteria may modify type 1 diabetes (T1D) development. However, the underlying mechanisms by which gut microbes could trigger or protect from diabetes are not fully understood, especially the interaction of commensal bacteria with pathogenic CD8 T cells. In this study, using islet-specific glucose-6-phosphatase catalytic subunit–related protein (IGRP)–reactive CD8 T cell receptor NY8.3 transgenic nonobese diabetic mice, we demonstrated that MyD88 strongly modulates CD8(+) T cell–mediated T1D development via the gut microbiota. Some microbial protein peptides share significant homology with IGRP. Both the microbial peptide mimic of Fusobacteria and the bacteria directly activate IGRP-specific NY8.3 T cells and promote diabetes development. Thus, we provide evidence of molecular mimicry between microbial antigens and an islet autoantigen and a novel mechanism by which the diabetogenicity of CD8(+) T cells can be regulated by innate immunity and the gut microbiota. The Rockefeller University Press 2016-09-19 /pmc/articles/PMC5030808/ /pubmed/27621416 http://dx.doi.org/10.1084/jem.20160526 Text en © 2016 Tai et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Tai, Ningwen Peng, Jian Liu, Fuqiang Gulden, Elke Hu, Youjia Zhang, Xiaojun Chen, Li Wong, F. Susan Wen, Li Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice |
title | Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice |
title_full | Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice |
title_fullStr | Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice |
title_full_unstemmed | Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice |
title_short | Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice |
title_sort | microbial antigen mimics activate diabetogenic cd8 t cells in nod mice |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030808/ https://www.ncbi.nlm.nih.gov/pubmed/27621416 http://dx.doi.org/10.1084/jem.20160526 |
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