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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
著者
佐藤, 真美 徳島大学大学院口腔科学研究科(口腔科学専攻)
Tawara, Hiroaki Tokushima University
Nagao, Ruka Tokushima University
Tanaka, Hidetaka Tokushima University
Tamura, Kai Tokushima University
Kawahito, Yuhki Tokushima University
キーワード
NK cell
IFN-γ
T cell
autoimmunity
Sjögren’s syndrome
資料タイプ
学位論文
抄録
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.
掲載誌名
Frontiers in Medicine
ISSN
2296858X
出版者
Frontiers Media S.A.
9
開始ページ
1036787
発行日
2022-10-26
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Mami Satoの学位論文として提出され,学位審査・授与の対象となっている。
権利情報
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.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3710号
学位記番号
甲口第489号
学位授与年月日
2023-03-23
学位名
博士(歯学)
学位授与機関
徳島大学
部局
歯学系
ポストLEDフォトニクス研究所
医学系