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Intestinal CXCR6+ ILC3s migrate to the kidney and exacerbate renal fibrosis via IL-23 receptor signaling enhanced by PD-1 expression.
Liang, Zhou; Tang, Ziwen; Zhu, Changjian; Li, Feng; Chen, Shuaijiabin; Han, Xu; Zheng, Ruilin; Hu, Xinrong; Lin, Ruoni; Pei, Qiaoqiao; Yin, Changjun; Wang, Ji; Tang, Ce; Cao, Nan; Zhao, Jincun; Wang, Rong; Li, Xiaoyan; Luo, Ning; Wen, Qiong; Yu, Jianwen; Li, Jianbo; Xia, Xi; Zheng, Xunhua; Wang, Xin; Huang, Naya; Zhong, Zhong; Mo, Chengqiang; Chen, Peisong; Wang, Yating; Fan, Jinjin; Guo, Yun; Zhong, Haojie; Liu, Jiaqi; Peng, Zhenwei; Mao, Haiping; Shi, Guo-Ping; Bonventre, Joseph V; Chen, Wei; Zhou, Yi.
Affiliation
  • Liang Z; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Tang Z; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Zhu C; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Li F; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Chen S; State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • Han X; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Zheng R; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Hu X; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Lin R; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Pei Q; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Yin C; Precision Medicine Research Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • Wang J; Precision Medicine Research Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • Tang C; Precision Medicine Research Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • Cao N; Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangzhou 510080, China.
  • Zhao J; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China.
  • Wang R; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Li X; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Luo N; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Wen Q; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Yu J; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Li J; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Xia X; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Zheng X; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Wang X; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Huang N; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Zhong Z; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Mo C; Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
  • Chen P; Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • Wang Y; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Fan J; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Guo Y; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Zhong H; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Liu J; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Peng Z; Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • Mao H; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
  • Shi GP; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Bonventre JV; Department of Nephrology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: jbonventre@bwh.harvard.edu.
  • Chen W; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China. Electronic address: chenwei99@mail.sysu.edu.cn.
  • Zhou Y; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China. Electronic address: zhouyi39@mail.sysu.edu.cn.
Immunity ; 57(6): 1306-1323.e8, 2024 Jun 11.
Article in En | MEDLINE | ID: mdl-38815582
ABSTRACT
Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Fibrosis / Lymphocytes / Signal Transduction / Cell Movement / Receptors, Interleukin / Programmed Cell Death 1 Receptor / Receptors, CXCR6 / Kidney Limits: Animals / Humans Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2024 Document type: Article Affiliation country: Country of publication:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Fibrosis / Lymphocytes / Signal Transduction / Cell Movement / Receptors, Interleukin / Programmed Cell Death 1 Receptor / Receptors, CXCR6 / Kidney Limits: Animals / Humans Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2024 Document type: Article Affiliation country: Country of publication: