Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA.
Department of Medicine, Rutgers New Jersey Medical School, Rutgers University, Newark, NJ, USA.
Nat Commun. 2021 Jun 7;12(1):3371. doi: 10.1038/s41467-021-23587-x.
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 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.
p53 在肿瘤抑制中的作用已经得到了广泛的研究和充分的证实。然而，p53 在寄生虫感染和肠道 2 型免疫中的作用尚不清楚。在这里，我们报告 p53 对于肠道 2 型免疫反应寄生虫感染（如鼠毛滴虫和巴西旋毛虫）至关重要。在机制上，p53 在毛细胞-IL-25-2 型先天淋巴细胞回路的激活中发挥关键作用，部分通过毛细胞中 Lrmp 的转录调控。Lrmp 调节 Ca2+内流和 IL-25 的释放，这是 2 型先天淋巴细胞反应的关键触发因素。因此，我们的研究结果揭示了 p53 在调节肠道 2 型免疫以抵御寄生虫感染中的一个先前未被认识到的功能，强调了 p53 作为免疫完整性守护者的作用。
