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Mineralocorticoid promotes intestinal inflammation through receptor dependent IL17 production in ILC3s.
Zhao, Rongchuan; Hong, Lei; Shi, Guohua; Ye, Hong; Lou, Xinqi; Zhou, Xinying; Yao, Jinyu; Shi, Xiaohua; An, Jianzhong; Sun, Minxuan.
Afiliación
  • Zhao R; School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230006, China; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou 215163, China.
  • Hong L; School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230006, China; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou 215163, China; Institute of Clinical Medicine Research,
  • Shi G; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou 215163, China.
  • Ye H; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou 215163, China.
  • Lou X; Institute of Clinical Medicine Research, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University. Suzhou Science and Technology Town Hospital. No. 1 Lijiang Road, Suzhou 215153, China.
  • Zhou X; School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230006, China; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou 215163, China.
  • Yao J; School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230006, China; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou 215163, China.
  • Shi X; Digestive Department, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou Science and Technology Town Hospital, No. 1 Lijiang Road, Suzhou 215153, China.
  • An J; Institute of Clinical Medicine Research, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University. Suzhou Science and Technology Town Hospital. No. 1 Lijiang Road, Suzhou 215153, China. Electronic address: szkjcyy_ajz@126.com.
  • Sun M; School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230006, China; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou 215163, China. Electronic address: minxuan.sun@sibet.ac
Int Immunopharmacol ; 130: 111678, 2024 Mar 30.
Article en En | MEDLINE | ID: mdl-38368773
ABSTRACT
Aldosterone is a key mineralocorticoid involved in regulating the concentration of blood electrolytes and physiological volume balance. Activation of mineralocorticoid receptor (MR) has been recently reported to participate in adaptive and innate immune responses under inflammation. Here, we evaluated the role of aldosterone and MR in inflammation bowel diseases (IBD). Aldosterone elevated in the colon of DSS-induced colitis mice. Aldosterone addition induced IL17 production and ROS/RNS level in group 3 innate lymphoid cells (ILC3s) and exacerbated intestinal injury. A selective mineralocorticoid receptor antagonism, eplerenone, inhibited IL17-producing ILC3s and its ROS/RNS production, protected mice from DSS-induced colitis. Mice lacking Nr3c2 (MR coding gene) in ILC3s exhibited decreased IL17 and ROS/RNS production, which alleviated colitis and colitis-associated colorectal cancer (CAC). Further experiments revealed that MR could directly bind to IL17A promoter and facilitate its transcription, which could be enhanced by aldosterone. Thus, our findings demonstrated the critical role of aldosterone-MR-IL17 signaling in ILC3s and gut homeostasis, indicating the therapeutic strategy of eplerenone in IBD clinical trial.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Colitis Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Colitis Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos