Bile acid-dependent transcription factors and chromatin accessibility determine regional heterogeneity of intestinal antimicrobial peptides.

Autor: Wang Y; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China., Yu Y; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China.; Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, China.; Shandong Provincial Clinical Research Center for digestive disease, Jinan, China., Li L; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China.; Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, China.; Shandong Provincial Clinical Research Center for digestive disease, Jinan, China., Zheng M; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China., Zhou J; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China., Gong H; School of Computer Science and Engineering, Sun Yat-sen University, Guangzhou, China., Feng B; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China., Wang X; Department of Pathology, Qilu Hospital of Shandong University, Jinan, China., Meng X; State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China., Cui Y; Advanced Medical Research Institute, Shandong University, Jinan, China., Xia Y; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China., Chu S; Advanced Medical Research Institute, Shandong University, Jinan, China., Lin L; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China., Chang H; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China., Zhou R; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China., Ma M; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China., Li Z; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China.; Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, China.; Shandong Provincial Clinical Research Center for digestive disease, Jinan, China., Ji R; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China.; Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, China.; Shandong Provincial Clinical Research Center for digestive disease, Jinan, China., Lu M; Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, China., Yang X; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China.; Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, China.; Shandong Provincial Clinical Research Center for digestive disease, Jinan, China., Zuo X; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China. zuoxiuli@sdu.edu.cn.; Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, China. zuoxiuli@sdu.edu.cn.; Shandong Provincial Clinical Research Center for digestive disease, Jinan, China. zuoxiuli@sdu.edu.cn., Li S; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China. lishiyang@sdu.edu.cn.; Advanced Medical Research Institute, Shandong University, Jinan, China. lishiyang@sdu.edu.cn.; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, China. lishiyang@sdu.edu.cn., Li Y; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China. liyanqing@sdu.edu.cn.; Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, China. liyanqing@sdu.edu.cn.; Shandong Provincial Clinical Research Center for digestive disease, Jinan, China. liyanqing@sdu.edu.cn.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Aug 22; Vol. 14 (1), pp. 5093. Date of Electronic Publication: 2023 Aug 22.
DOI: 10.1038/s41467-023-40565-7
Abstrakt: Antimicrobial peptides (AMPs) are important mediators of intestinal immune surveillance. However, the regional heterogeneity of AMPs and its regulatory mechanisms remain obscure. Here, we clarified the regional heterogeneity of intestinal AMPs at the single-cell level, and revealed a cross-lineages AMP regulation mechanism that bile acid dependent transcription factors (BATFs), NR1H4, NR1H3 and VDR, regulate AMPs through a ligand-independent manner. Bile acids regulate AMPs by perturbing cell differentiation rather than activating BATFs signaling. Chromatin accessibility determines the potential of BATFs to regulate AMPs at the pre-transcriptional level, thus shaping the regional heterogeneity of AMPs. The BATFs-AMPs axis also participates in the establishment of intestinal antimicrobial barriers of fetuses and the defects of antibacterial ability during Crohn's disease. Overall, BATFs and chromatin accessibility play essential roles in shaping the regional heterogeneity of AMPs at pre- and postnatal stages, as well as in maintenance of antimicrobial immunity during homeostasis and disease.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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