首页|Cmtm4 deficiency exacerbates colitis by inducing gut dysbiosis and S100a8/9 expression

Cmtm4 deficiency exacerbates colitis by inducing gut dysbiosis and S100a8/9 expression

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The dysfunction of innate immunity components is one of the major drivers for ulcerative colitis(UC),and increasing reports indicate that the gut microbiome serves as an intermediate between genetic mutations and UC development.Here,we find that the IL-17 receptor subunit,CMTM4,is reduced in UC patients and dextran sulfate sodium(DSS)-induced colitis.The deletion of CMTM4(Cmtm4-/-)in mice leads to a higher susceptibility to DSS-induced colitis than in wild-type,and the gut microbiome significantly changes in composition.The causal role of the gut microbiome is confirmed with a cohousing experiment.We further identify that S100a8/9 is significantly up-regulated in Cmtm4-/-colitis,with the block of its receptor RAGE that reverses the phenotype associated with the CMTM4 deficiency.CMTM4 deficiency rather suppresses S100a8/9 expression in vitro via the IL17 pathway,further supporting that the elevation of S100a8/9 in vivo is most likely a result of microbial dysbiosis.Taken together,the results suggest that CMTM4 is involved in the maintenance of intestinal homeostasis,suppression of S100a8/9,and prevention of colitis development.Our study further shows CMTM4 as a crucial innate immunity component,confirming its important role in UC development and providing insights into potential targets for the development of future therapies.

Ulcerative colitisCMTM4Gut microbiotaIL-17 receptor C(IL-17RC)S100a8/9

Qiao Meng、Jing Ning、Jingjing Lu、Jing Zhang、Ming Zu、Xiurui Han、Huiling Zheng、Yueqing Gong、Xinyu Hao、Ying Xiong、Fang Gu、Wenling Han、Weiwei Fu、Jun Wang、Shigang Ding

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Department of Gastroenterology,Peking University Third Hospital,Beijing 100191,China

Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases(BZ0371),Beijing 100191,China

CAS Key Laboratory of Pathogenic Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,Beijing 100101,China

University of Chinese Academy of Sciences,Beijing 100101,China

Department of Immunology,School of Basic Medical Sciences,Peking University Health Science Center,NHC Key Laboratory of Medical Immunology(Peking University),Beijing 100191,China

Peking University Center for Human Disease Genomics,Beijing 100191,China

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National Natural Science Foundation of ChinaStrategic Priority Research Program of the Chinese Academy of Sciences

81870386XDB29020000

2024

10.1016/j.jgg.2024.03.009

遗传学报
中国遗传学会 中国科学院遗传与发育生物学研究所

遗传学报

CSTPCD
影响因子：0.821
ISSN：1673-8527
年,卷(期)：2024.51(8)