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Title: Modulation of autoimmune pathogenesis by T cell-triggered inflammatory cell death
Authors: Sasaki, Katsuhiro
Himeno, Ai
Nakagawa, Tomoko
Sasaki, Yoshiteru
Kiyonari, Hiroshi
Iwai, Kazuhiro
Author's alias: 佐々木, 克博
中川, 朋子
佐々木, 義輝
清成, 寛
岩井, 一宏
Keywords: Cell death and immune response
Inflammation
Regulatory T cells
Ubiquitylation
Issue Date: 28-Aug-2019
Publisher: Springer Nature
Journal title: Nature Communications
Volume: 10
Thesis number: 3878
Abstract: T cell-mediated autoimmunity encompasses diverse immunopathological outcomes; however, the mechanisms underlying this diversity are largely unknown. Dysfunction of the tripartite linear ubiquitin chain assembly complex (LUBAC) is associated with distinct autonomous immune-related diseases. Cpdm mice lacking Sharpin, an accessory subunit of LUBAC, have innate immune cell-predominant dermatitis triggered by death of LUBAC-compromised keratinocytes. Here we show that specific gene ablation of Sharpin in mouse Treg causes phenotypes mimicking cpdm-like inflammation. Mechanistic analyses find that multiple types of programmed cell death triggered by TNF from tissue-oriented T cells initiate proinflammatory responses to implicate innate immune-mediated pathogenesis in this T cell-mediated inflammation. Moreover, additional disruption of the Hoip locus encoding the catalytic subunit of LUBAC converts cpdm-like dermatitis to T cell-predominant autoimmune lesions; however, innate immune-mediated pathogenesis still remains. These findings show that T cell-mediated killing and sequential autoinflammation are common and crucial for pathogenic diversity during T cell-mediated autoimmune responses.
Description: 自己免疫疾患の新たな病態発症メカニズムを解明 --炎症性疾患におけるT細胞の新たな役割--. 京都大学プレスリリース. 2019-09-06.
Rights: © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
URI: http://hdl.handle.net/2433/243883
DOI(Published Version): 10.1038/s41467-019-11858-7
PubMed ID: 31462647
Related Link: http://www.kyoto-u.ac.jp/ja/research/research_results/2019/190828_2.html
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