マツイ　タケシ   Takeshi Matsui   松井　毅    所属   応用生物学部 応用生物学科    職種   教授
言語種別	英語
発行・発表の年月	2021/12
形態種別	学術論文
査読	査読あり
標題	Peripheral tolerance by Treg via constraining OX40 signal in autoreactive T cells against desmoglein 3, a target antigen in pemphigus
執筆形態	共著
掲載誌名	Proceedings of the National Academy of Sciences of United States of America
掲載区分	国外
出版社・発行元	National Academy of Sciences
巻・号・頁	118(49),pp.e2026763118
著者・共著者	Hisato Iriki, Hayato Takahashi, Naoko Wada, Hisashi Nomura, Miho Mukai, Aki Kamata, Hiromi Ito, Jun Yamagami, Takeshi Matsui, Yutaka Kurebayashi, Setsuko Mise-Omata, Hiroshi Nishimasu, Osamu Nureki, Akihiko Yoshimura, Shohei Hori, Masayuki Amagai
概要	Immune tolerance is crucial to prevent harmful immune reactions against self-antigens and well operated by central thymic tolerance and peripheral tissue tolerance. However, peripheral tolerance had been investigated under influence from thymic tolerance. We successfully decoupled peripheral tolerance from thymic tolerance by utilizing autoantigen-deficient thymus. Experiments revealed that self-antigen presentation in steady state initiated proliferation but subsequent disappearance of autoreactive CD4+ T cells in draining lymph nodes. After screening of representative candidates, including Ctla4, autoimmune regulator, and Pd-1, the mechanism was found to depend on regulatory T cell (Treg) function that constrained OX40 signaling of the T cells. This study presented fundamental, but potent, Treg-mediated tolerance mechanisms of peripheral tissues to prevent autoimmunity as compensatory roles for central tolerance.