Tumor suppressor p53 regulates intestinal type 2 immunity

被引：31

作者：

Chang, Chun-Yuan ^{[1
]}

Wang, Jianming ^{[1
]}

Zhao, Yuhan ^{[1
]}

Liu, Juan ^{[1
]}

Yang, Xue ^{[1
]}

Yue, Xuetian ^{[1
]}

Wang, Huaying ^{[1
]}

Zhou, Fan ^{[1
]}

Inclan-Rico, Juan M. ^{[2
]}

Ponessa, John J. ^{[2
]}

Xie, Ping ^{[3
]}

Zhang, Lanjing ^{[1
,4
]}

Siracusa, Mark C. ^{[2
]}

Feng, Zhaohui ^{[1
]}

Hu, Wenwei ^{[1
]}

机构：

[1] Rutgers State Univ, Rutgers Canc Inst New Jersey, New Brunswick, NJ 08901 USA

[2] Rutgers State Univ, Rutgers New Jersey Med Sch, Dept Med, Newark, NJ USA

[3] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ USA

[4] Penn Med Princeton Med Ctr, Dept Pathol, Plainsboro, NJ USA

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

关键词：

TUFT CELLS; MUTANT P53; GENE; RESPONSES; ANTIGEN; PROTEIN; CANCER; IL-13;

D O I：

10.1038/s41467-021-23587-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. P53 is a well-known tumour suppressor, however its role in intestinal type 2 immunity is currently unclear. Here authors report that during parasitic infections, p53 triggers tuft cell Ca2+ influx and IL-25 release, and shows a regulatory role for p53 in intestinal type 2 immunity via transcriptional regulation of the Lrmp gene.

引用

页数：13

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