Group 3 Innate Lymphoid Cells Exacerbate Lupus Nephritis by Promoting B Cell Activation in Kidney Ectopic Lymphoid Structures
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Published:2023-11
Issue:35
Volume:10
Page:
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ISSN:2198-3844
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Container-title:Advanced Science
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language:en
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Short-container-title:Advanced Science
Author:
Li Feng12ORCID, Liang Zhou12ORCID, Zhong Haojie23ORCID, Hu Xinrong12, Tang Ziwen12, Zhu Changjian12, Shen Jiani12, Han Xu12, Lin Ruoni12, Zheng Ruilin12, Tang Ruihan12, Peng Huajing12, Zheng Xunhua12, Mo Chengqiang4, Chen Peisong5, Wang Xin12, Wen Qiong12, Li Jianbo12, Xia Xi12, Ye Hongjian12, Qiu Yagui12, Yu Jianwen12, Fu Dongying12, Liu Jiaqi12, Wang Rong12, Xie Huixin12, Guo Yun12, Li Xiaoyan12, Fan Jinjin12, Liu Qinghua12, Mao Haiping12, Chen Wei12, Zhou Yi12ORCID
Affiliation:
1. Department of Nephrology The First Affiliated Hospital, Sun Yat‐sen University Guangzhou 510080 China 2. NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of Nephrology Guangzhou 510080 China 3. Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital, Shenzhen University Shenzhen 518000 China 4. Department of Urology The First Affiliated Hospital, Sun Yat‐sen University Guangzhou 510080 China 5. Department of Laboratory Medicine The First Affiliated Hospital, Sun Yat‐sen University Guangzhou 510080 China
Abstract
AbstractGroup 3 innate lymphoid cells (ILC3s) represent a new population in immune regulation, yet their role in lupus nephritis (LN) remains elusive. In the present work, systemic increases in ILC3s, particularly in the kidney, are observed to correlate strongly with disease severity in both human and murine LN. Using MRL/lpr lupus mice and a nephrotoxic serum‐induced LN model, this study demonstrates that ILC3s accumulated in the kidney migrate predominantly from the intestine. Furthermore, intestinal ILC3s accelerate LN progression, manifested by exacerbated autoimmunity and kidney injuries. In LN kidneys, ILC3s are located adjacent to B cells within ectopic lymphoid structures (ELS), directly activating B cell differentiation into plasma cells and antibody production in a Delta‐like1 (DLL1)/Notch‐dependent manner. Blocking DLL1 attenuates ILC3s’ effects and protects against LN. Altogether, these findings reveal a novel pathogenic role of ILC3s in B cell activation, renal ELS formation and autoimmune injuries during LN, shedding light on the therapeutic value of targeting ILC3s for LN.
Funder
National Natural Science Foundation of China Guangdong Special Support Plan Natural Science Foundation of Guangdong Province
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)
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