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Dysregulation of Wnt/β-catenin signaling contributes to intestinal inflammation through regulation of group 3 innate lymphoid cells

Author

Listed:
  • Jiacheng Hao

    (Tsinghua University
    Tsinghua University
    Tsinghua University
    Tsinghua University)

  • Chang Liu

    (Tsinghua University)

  • Zhijie Gu

    (Tsinghua University
    Tsinghua University
    Tsinghua University
    Tsinghua University)

  • Xuanming Yang

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

  • Xun Lan

    (Tsinghua University
    Tsinghua University)

  • Xiaohuan Guo

    (Tsinghua University
    Tsinghua University
    Tsinghua University)

Abstract

RORγt+ group 3 innate lymphoid cells (ILC3s) are essential for intestinal homeostasis. Dysregulation of ILC3s has been found in the gut of patients with inflammatory bowel disease and colorectal cancer, yet the specific mechanisms still require more investigation. Here we observe increased β-catenin in intestinal ILC3s from inflammatory bowel disease and colon cancer patients compared with healthy donors. In contrast to promoting RORγt expression in T cells, activation of Wnt/β-catenin signaling in ILC3s suppresses RORγt expression, inhibits its proliferation and function, and leads to a deficiency of ILC3s and subsequent intestinal inflammation in mice. Activated β-catenin and its interacting transcription factor, TCF-1, cannot directly suppress RORγt expression, but rather alters global chromatin accessibility and inhibits JunB expression, which is essential for RORγt expression in ILC3s. Together, our findings suggest that dysregulated Wnt/β-catenin signaling impairs intestinal ILC3s through TCF-1/JunB/RORγt regulation, further disrupting intestinal homeostasis, and promoting inflammation and cancer.

Suggested Citation

  • Jiacheng Hao & Chang Liu & Zhijie Gu & Xuanming Yang & Xun Lan & Xiaohuan Guo, 2024. "Dysregulation of Wnt/β-catenin signaling contributes to intestinal inflammation through regulation of group 3 innate lymphoid cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45616-1
    DOI: 10.1038/s41467-024-45616-1
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    1. Lei Zhou & Coco Chu & Fei Teng & Nicholas J. Bessman & Jeremy Goc & Endi K. Santosa & Gregory G. Putzel & Hiroki Kabata & Judith R. Kelsen & Robert N. Baldassano & Manish A. Shah & Robbyn E. Sockolow , 2019. "Innate lymphoid cells support regulatory T cells in the intestine through interleukin-2," Nature, Nature, vol. 568(7752), pages 405-409, April.
    2. Zafrul Hasan & Shin-ichi Koizumi & Daiki Sasaki & Hayato Yamada & Nana Arakaki & Yoshitaka Fujihara & Shiho Okitsu & Hiroki Shirahata & Hiroki Ishikawa, 2017. "JunB is essential for IL-23-dependent pathogenicity of Th17 cells," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    3. Mengze Lyu & Hiroaki Suzuki & Lan Kang & Fabrina Gaspal & Wenqing Zhou & Jeremy Goc & Lei Zhou & Jordan Zhou & Wen Zhang & Zeli Shen & James G. Fox & Robbyn E. Sockolow & Terri M. Laufer & Yong Fan & , 2022. "ILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut," Nature, Nature, vol. 610(7933), pages 744-751, October.
    4. Matthew R. Hepworth & Laurel A. Monticelli & Thomas C. Fung & Carly G. K. Ziegler & Stephanie Grunberg & Rohini Sinha & Adriana R. Mantegazza & Hak-Ling Ma & Alison Crawford & Jill M. Angelosanto & E., 2013. "Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria," Nature, Nature, vol. 498(7452), pages 113-117, June.
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