Nature Communications (Aug 2023)

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,
  • Yanqing Li

DOI
https://doi.org/10.1038/s41467-023-40565-7
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 16

Abstract

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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.