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タイトル: | CD153/CD30 signaling promotes age-dependent tertiary lymphoid tissue expansion and kidney injury |
著者: | Sato, Yuki Oguchi, Akiko Fukushima, Yuji Masuda, Kyoko Toriu, Naoya Taniguchi, Keisuke Yoshikawa, Takahisa Cui, Xiaotong Kondo, Makiko Hosoi, Takeshi Komidori, Shota Shimizu, Yoko Fujita, Harumi Jiang, Li Kong, Yingyi Yamanashi, Takashi Seita, Jun Yamamoto, Takuya https://orcid.org/0000-0002-0022-3947 (unconfirmed) Toyokuni, Shinya Hamazaki, Yoko Hattori, Masakazu Yoshikai, Yasunobu Boor, Peter Floege, Jürgen Kawamoto, Hiroshi Murakawa, Yasuhiro Minato, Nagahiro Yanagita, Motoko https://orcid.org/0000-0002-0339-9008 (unconfirmed) |
著者名の別形: | 佐藤, 有紀 小口, 綾貴子 福島, 祐二 増田, 喬子 鳥生, 直哉 谷口, 圭祐 好川, 貴久 崔, 笑桐 近藤, 麻紀子 小緑, 翔太 清水, 葉子 藤田, 春美 山梨, 貴士 清田, 純 山本, 拓也 豊國, 伸哉 濵﨑, 洋子 服部, 雅一 吉開, 康信 河本, 宏 村川, 泰裕 湊, 長博 柳田, 素子 |
発行日: | 18-Jan-2022 |
出版者: | American Society for Clinical Investigation |
誌名: | Journal of Clinical Investigation |
巻: | 132 |
号: | 2 |
論文番号: | e146071 |
抄録: | Tertiary lymphoid tissues (TLTs) facilitate local T- and B-cell interactions in chronically inflamed organs. However, the cells and molecular pathways that govern TLT formation are poorly defined. Here we identify TNF superfamily CD153-CD30 signaling between two unique age-dependent lymphocyte subpopulations, CD153⁺PD-1⁺CD4⁺ senescence-associated T (SAT) cells and CD30+T-bet+ age-associated B cells (ABCs), as a driver for TLT expansion. SAT cells, which produced ABC-inducing factors IL21 and IFNγ, and ABCs progressively accumulated within TLTs in aged kidneys after injury. Notably, in kidney injury models, CD153 or CD30 deficiency impaired functional SAT cell induction, which resulted in reduced ABC numbers and attenuated TLT formation with improved inflammation, fibrosis and renal function. Attenuated TLT formation after transplantation of CD153-deficient bone marrow further supported the importance of CD153 in immune cells. Clonal analysis revealed that SAT cells and ABCs in the kidneys arose from both local differentiation and recruitment from the spleen. In the synovium of aged rheumatoid arthritis patients, T peripheral helper/T follicular helper cells and ABCs also expressed CD153 and CD30, respectively. Together, our data reveal a previously unappreciated function of CD153-CD30 signaling in TLT formation and propose targeting CD153-CD30 signaling pathway as a therapeutic target for slowing kidney disease progression. |
記述: | 高齢者腎臓病を悪化させる原因細胞・分子の同定に成功. 京都大学プレスリリース. 2021-11-30. A new drug target for kidney disease. 京都大学プレスリリース. 2021-11-30. |
著作権等: | © 2022, Sato et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. |
URI: | http://hdl.handle.net/2433/267527 |
DOI(出版社版): | 10.1172/JCI146071 |
PubMed ID: | 34813503 |
関連リンク: | https://ashbi.kyoto-u.ac.jp/ja/news/20211130_research-result_yanagita/ https://ashbi.kyoto-u.ac.jp/news/20211130_research-result_yanagita/ |
出現コレクション: | 学術雑誌掲載論文等 |
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