Circadian Clock Disruption Suppresses PDL1+ Intraepithelial B Cells in Experimental Colitis and Colitis-Associated Colorectal Cancer
Jinglin Liu, Chuyi Wang, Tianyu Cheng, Youlutuziayi Rixiati, Cheng Ji, Min Deng, Su Yao, Lihua Yuan, Yuanyuan Zhao, Tong Shen, Jian‐Ming Li
Abstract
BACKGROUND & AIMS: The circadian clock is crucial for physiological homeostasis including gut homeostasis. Disorder of the circadian clock may contribute to many diseases including inflammatory bowel disease (IBD). However, the role and the mechanisms of circadian clock involvement in IBD still are unclear. METHODS: ) were established. Dextran sulfate sodium (DSS) and/or azoxymethane were used to induce mouse models of colitis and its associated colorectal cancer. Flow cytometry, immunohistochemistry, immunofluorescence, Western blot, and reverse-transcription quantitative polymerase chain reaction were used to analyze the characteristics of immune cells and their related molecules. RESULTS: T cells promoted colitis-associated colorectal cancer (CRC) in mice. In clinical samples from CRC patients, low expression of Bmal1 gene in paracancerous tissues and center area of tumor was associated closely with a poorer prognosis of CRC patients. CONCLUSIONS: cells of IELs in IBD and IBD-associated CRC.