Tumor suppressor p53 regulates intestinal type 2 immunity
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, Zhaohui Feng, Wenwei Hu
Abstract
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 2+ 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.