Disturbed natural killer cell homeostasis in the salivary gland enhances autoimmune pathology via IFN-γ in a mouse model of primary Sjögren’s syndrome

• 資料種別: 博士論文
• タイトル: Disturbed natural killer cell homeostasis in the salivary gland enhances autoimmune pathology via IFN-γ in a mouse model of primary Sjögren’s syndrome
• 著者・編者: Sato, Mami; Arakaki, Rieko; Tawara, Hiroaki; Nagao, Ruka; Tanaka, Hidetaka; Tamura, Kai; Kawahito, Yuhki; Otsuka, Kunihiro; Ushio, Aya; Tsunematsu, Takaaki; Ishimaru, Naozumi
• 著者標目: Sato, Mami; Arakaki, Rieko; Tawara, Hiroaki; Nagao, Ruka; Tanaka, Hidetaka; Tamura, Kai; Kawahito, Yuhki; Otsuka, Kunihiro; Ushio, Aya; Tsunematsu, Takaaki; Ishimaru, Naozumi
• 出版事項: Frontiers Media S.A.
• 出版年月日等: 2022-10-26
• 出版年（W3CDTF）: 2022-10-26
• 並列タイトル等: 原発性シェーグレン症候群モデルマウスにおいて唾液腺Natural killer細胞の恒常性の破綻がIFN-γを介して自己免疫病変を増強する
• タイトル（掲載誌）: Frontiers in Medicine
• 巻号年月日等（掲載誌）: 9
• 掲載巻: 9
• 掲載ページ: 1036787-
• ISSN（掲載誌）: ISSN : 2296-858X
• 授与機関名: 徳島大学
• 授与年月日: 2023-03-23
• 報告番号: 甲第3710号
• 学位: 博士（歯学）
• 本文の言語コード: eng
• 件名標目: NK cell; IFN-γ; T cell; autoimmunity; Sjögren’s syndrome
• 対象利用者: 一般
• 一般注記: Objective: Innate lymphoid cells (ILCs), including natural killer (NK) cells, ILC1, ILC2, lymphoid tissue-inducer (LTi) cells, and ILC3 cell, play a key role in various immune responses. Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by chronic inflammation of exocrine glands, such as the lacrimal and salivary glands (SGs). The role of NK cells among ILCs in the pathogenesis of pSS is still unclear. In this study, the characteristics and subsets of NK cells in the salivary gland (SG) tissue were analyzed using a murine model of pSS. Methods: Multiple phenotypes and cytotoxic signature of the SG NK cells in control and pSS model mice were evaluated by flow cytometric analysis. Intracellular expression of interferon-γ (IFN-γ) among T cells and NK cells from the SG tissues was compared by in vitro experiments. In addition, pathological analysis was performed using anti-asialo-GM1 (ASGM1) antibody (Ab)-injected pSS model mice. Results: The number of conventional NK (cNK) cells in the SG of pSS model mice significantly increased compared with that in control mice at 6 weeks of age. The production level of IFN-γ was significantly higher in SG NK cells than in SG T cells. The depletion of NK cells by ASGM1 Ab altered the ratio of tissue resident NK (rNK) cells to cNK cells, which inhibited the injury to SG cells with the recovery of saliva secretion in pSS model mice. Conclusion: The results indicate that SG cNK cells may enhance the autoreactive response in the target organ by upregulating of IFN-γ, whereas SG rNK cells protect target cells against T cell cytotoxicity. Therefore, the activation process and multiple functions of NK cells in the target organ could be helpful to develop potential markers for determining autoimmune disease activity and target molecules for incurable immune disorders.
• オンライン閲覧公開範囲: インターネット公開
• 著作権情報: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
• 関連情報（DOI）: 10.3389/fmed.2022.1036787
• 連携機関・データベース: 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• 提供元機関・データベース: 徳島大学 : 徳島大学機関リポジトリ

目次

http://repo.lib.tokushima-u.ac.jp/files/public/11/118305/20230607162126156170/k3710_abstract.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/118305/20230607162126306256/k3710_review.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/118305/20230607162126427448/k3710_fulltext.pdf fulltext