학술논문
Apoptosis in response to microbial infection induces autoreactive TH17 cells
Document Type
Report
Author
Source
Nature Immunology. September 2016, Vol. 17 Issue 9, p1084, 9 p.
Subject
Language
English
ISSN
1529-2908
Abstract
Author(s): Laura Campisi; Gaetan Barbet [1, 2]; Yi Ding [3]; Enric Esplugues [4]; Richard A Flavell [4]; J Magarian Blander (corresponding author) [1, 2, 5, 6] Autoimmunity is caused by [...]
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[sup.+] 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 T[sub.H]17 subset of helper T cells, prominently associated with autoimmune disease. Once induced, the self-reactive T[sub.H]17 cells promoted auto-inflammation and autoantibody generation. Our findings have implications for how infections precipitate autoimmunity.
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[sup.+] 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 T[sub.H]17 subset of helper T cells, prominently associated with autoimmune disease. Once induced, the self-reactive T[sub.H]17 cells promoted auto-inflammation and autoantibody generation. Our findings have implications for how infections precipitate autoimmunity.