Tumor suppressor p53 regulates intestinal type 2 immunity.

Chang, Chun-Yuan; Wang, Jianming; Zhao, Yuhan; Liu, Juan; Yang, Xue; Yue, Xuetian; Wang, Huaying; Zhou, Fan et al. · Nat Commun · 2021

basic_science · Level V

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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 Ca<sup>2+</sup> 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.

Medical subject headings