Group 3 Innate Lymphoid Cells Exacerbate Lupus Nephritis by Promoting B Cell Activation in Kidney Ectopic Lymphoid Structures

Feng Li; Zhou Liang; Haojie Zhong; Xinrong Hu; Ziwen Tang; Changjian Zhu; Jiani Shen; Xu Han; Ruoni Lin; Ruilin Zheng; Ruihan Tang; Huajing Peng; Xunhua Zheng; Chengqiang Mo; Peisong Chen; Xin Wang; Qiong Wen; Jianbo Li; Xi Xia; Hongjian Ye; Yagui Qiu; Jianwen Yu; Dongying Fu; Jiaqi Liu; Rong Wang; Huixin Xie; Yun Guo; Xiaoyan Li; Jinjin Fan; Qinghua Liu; Haiping Mao; Wei Chen; Yi Zhou

doi:10.1002/advs.202302804

Group 3 Innate Lymphoid Cells Exacerbate Lupus Nephritis by Promoting B Cell Activation in Kidney Ectopic Lymphoid Structures

Adv Sci (Weinh). 2023 Dec;10(35):e2302804. doi: 10.1002/advs.202302804. Epub 2023 Nov 1.

Authors

Feng Li^{1

2}, Zhou Liang^{1

2}, Haojie Zhong^{2

3}, Xinrong Hu^{1

2}, Ziwen Tang^{1

2}, Changjian Zhu^{1

2}, Jiani Shen^{1

2}, Xu Han^{1

2}, Ruoni Lin^{1

2}, Ruilin Zheng^{1

2}, Ruihan Tang^{1

2}, Huajing Peng^{1

2}, Xunhua Zheng^{1

2}, Chengqiang Mo⁴, Peisong Chen⁵, Xin Wang^{1

2}, Qiong Wen^{1

2}, Jianbo Li^{1

2}, Xi Xia^{1

2}, Hongjian Ye^{1

2}, Yagui Qiu^{1

2}, Jianwen Yu^{1

2}, Dongying Fu^{1

2}, Jiaqi Liu^{1

2}, Rong Wang^{1

2}, Huixin Xie^{1

2}, Yun Guo^{1

2}, Xiaoyan Li^{1

2}, Jinjin Fan^{1

2}, Qinghua Liu^{1

2}, Haiping Mao^{1

2}, Wei Chen^{1

2}, Yi Zhou^{1

2}

Affiliations

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

Group 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.

Keywords: B cells; ectopic lymphoid structures; group 3 innate lymphoid cells; lupus nephritis.

MeSH terms

Animals
Humans
Immunity, Innate
Kidney
Lupus Nephritis* / drug therapy
Lupus Nephritis* / pathology
Lymphocytes
Mice
Mice, Inbred MRL lpr

Abstract

MeSH terms

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