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Tumor suppressor p53 regulates intestinal type 2 immunity

Author

Listed:
  • Chun-Yuan Chang

    (Rutgers Cancer Institute of New Jersey, Rutgers University)

  • Jianming Wang

    (Rutgers Cancer Institute of New Jersey, Rutgers University)

  • Yuhan Zhao

    (Rutgers Cancer Institute of New Jersey, Rutgers University)

  • Juan Liu

    (Rutgers Cancer Institute of New Jersey, Rutgers University)

  • Xue Yang

    (Rutgers Cancer Institute of New Jersey, Rutgers University)

  • Xuetian Yue

    (Rutgers Cancer Institute of New Jersey, Rutgers University)

  • Huaying Wang

    (Rutgers Cancer Institute of New Jersey, Rutgers University)

  • Fan Zhou

    (Rutgers Cancer Institute of New Jersey, Rutgers University)

  • Juan M. Inclan-Rico

    (Rutgers New Jersey Medical School, Rutgers University)

  • John J. Ponessa

    (Rutgers New Jersey Medical School, Rutgers University)

  • Ping Xie

    (Rutgers University)

  • Lanjing Zhang

    (Rutgers Cancer Institute of New Jersey, Rutgers University
    Penn Medicine Princeton Medical Center)

  • Mark C. Siracusa

    (Rutgers New Jersey Medical School, Rutgers University)

  • Zhaohui Feng

    (Rutgers Cancer Institute of New Jersey, Rutgers University)

  • Wenwei Hu

    (Rutgers Cancer Institute of New Jersey, Rutgers University)

Abstract

The role of p53 in tumor suppression has been extensively studied and well-established. However, the role of p53 in parasitic infections and the intestinal type 2 immunity is unclear. Here, we report that p53 is crucial for intestinal type 2 immunity in response to the infection of parasites, such as Tritrichomonas muris and Nippostrongylus brasiliensis. Mechanistically, p53 plays a critical role in the activation of the tuft cell-IL-25-type 2 innate lymphoid cell circuit, partly via transcriptional regulation of Lrmp in tuft cells. Lrmp modulates Ca2+ influx and IL-25 release, which are critical triggers of type 2 innate lymphoid cell response. Our results thus reveal a previously unrecognized function of p53 in regulating intestinal type 2 immunity to protect against parasitic infections, highlighting the role of p53 as a guardian of immune integrity.

Suggested Citation

  • Chun-Yuan Chang & Jianming Wang & Yuhan Zhao & Juan Liu & Xue Yang & Xuetian Yue & Huaying Wang & Fan Zhou & Juan M. Inclan-Rico & John J. Ponessa & Ping Xie & Lanjing Zhang & Mark C. Siracusa & Zhaoh, 2021. "Tumor suppressor p53 regulates intestinal type 2 immunity," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23587-x
    DOI: 10.1038/s41467-021-23587-x
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    Cited by:

    1. Jianming Wang & Chun-Yuan Chang & Xue Yang & Fan Zhou & Juan Liu & Jill Bargonetti & Lanjing Zhang & Ping Xie & Zhaohui Feng & Wenwei Hu, 2024. "p53 suppresses MHC class II presentation by intestinal epithelium to protect against radiation-induced gastrointestinal syndrome," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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