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

Yue Wang, Yanbo Yu, Lixiang Li, Mengqi Zheng, Jiawei Zhou, Haifan Gong, Bingcheng Feng, Xiao Wang, Xuanlin Meng, Yanyan Cui, Yanan Xia, Shuzheng Chu, Lin Lin, Huijun Chang, Ruchen Zhou, Mingjun Ma, Zhen Li, Rui Ji, Ming Lu, Xiaoyun Yang, Xiuli Zuo (), Shiyang Li () and Yanqing Li ()
Additional contact information
Yue Wang: Qilu Hospital of Shandong University
Yanbo Yu: Qilu Hospital of Shandong University
Lixiang Li: Qilu Hospital of Shandong University
Mengqi Zheng: Qilu Hospital of Shandong University
Jiawei Zhou: Qilu Hospital of Shandong University
Haifan Gong: Sun Yat-sen University
Bingcheng Feng: Qilu Hospital of Shandong University
Xiao Wang: Qilu Hospital of Shandong University
Xuanlin Meng: Shanghai Jiao Tong University
Yanyan Cui: Shandong University
Yanan Xia: Qilu Hospital of Shandong University
Shuzheng Chu: Shandong University
Lin Lin: Qilu Hospital of Shandong University
Huijun Chang: Qilu Hospital of Shandong University
Ruchen Zhou: Qilu Hospital of Shandong University
Mingjun Ma: Qilu Hospital of Shandong University
Zhen Li: Qilu Hospital of Shandong University
Rui Ji: Qilu Hospital of Shandong University
Ming Lu: Qilu Hospital of Shandong University
Xiaoyun Yang: Qilu Hospital of Shandong University
Xiuli Zuo: Qilu Hospital of Shandong University
Shiyang Li: Qilu Hospital of Shandong University
Yanqing Li: Qilu Hospital of Shandong University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-40565-7

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