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- Title
Bile acid-dependent transcription factors and chromatin accessibility determine regional heterogeneity of intestinal antimicrobial peptides.
- Authors
Wang, Yue; Yu, Yanbo; Li, Lixiang; Zheng, Mengqi; Zhou, Jiawei; Gong, Haifan; Feng, Bingcheng; Wang, Xiao; Meng, Xuanlin; Cui, Yanyan; Xia, Yanan; Chu, Shuzheng; Lin, Lin; Chang, Huijun; Zhou, Ruchen; Ma, Mingjun; Li, Zhen; Ji, Rui; Lu, Ming; Yang, Xiaoyun
- 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. Wang et al. clarify the regional heterogeneity of intestinal AMPs and identify that chromatin accessibility determines the potential of BATFs to regulate AMPs at the pre-transcriptional level, thus shaping the regional heterogeneity of AMPs.
- Subjects
ANTIMICROBIAL peptides; FARNESOID X receptor; TRANSCRIPTION factors; VITAMIN D receptors; CROHN'S disease; CHROMATIN; HETEROGENEITY
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-40565-7