气候变化领域集成服务门户(CCPortal): Up-regulation of gasdermin C in mouse small intestine is associated with lytic cell death in enterocytes in worm-induced type 2 immunity

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DOI	10.1073/pnas.2026307118
	Up-regulation of gasdermin C in mouse small intestine is associated with lytic cell death in enterocytes in worm-induced type 2 immunity
	Xi R.; Montague J.; Lin X.; Lu C.; Lei W.; Tanaka K.; Zhang Y.V.; Xu X.; Zheng X.; Zhou X.; Urban J.F.; Iwatsuki K.; Margolskee R.F.; Matsumoto I.; Tizzano M.; Li J.; Jiang P.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:30
英文摘要	“Taste-like” tuft cells in the intestine trigger type 2 immunity in response to worm infection. The secretion of interleukin-13 (IL-13) from type 2 innate lymphoid cells (ILC2) represents a key step in the tuft cell–ILC2 cell–intestinal epithelial cell circuit that drives the clearance of worms from the gut via type 2 immune responses. Hallmark features of type 2 responses include tissue remodeling, such as tuft and goblet cell expansion, and villus atrophy, yet it remains unclear if additional molecular changes in the gut epithelium facilitate the clearance of worms from the gut. Using gut organoids, we demonstrated that IL-4 and IL-13, two type 2 cytokines with similar functions, not only induced the classical type 2 responses (e.g., tuft cell expansion) but also drastically up-regulated the expression of gasdermin C genes (Gsdmcs). Using an in vivo worm-induced type 2 immunity model, we confirmed the up-regulation of Gsdmcs in Nippostrongylus brasiliensis–infected wild-type C57BL/6 mice. Consistent with gasdermin family members being principal effectors of pyroptosis, overexpression of Gsdmc2 in human embryonic kidney 293 (HEK293) cells triggered pyroptosis and lytic cell death. Moreover, in intestinal organoids treated with IL-4 or IL-13, or in wild-type mice infected with N. brasiliensis, lytic cell death increased, which may account for villus atrophy observed in worm-infected mice. Thus, we propose that the up-regulated Gsdmc family may be major effectors for type 2 responses in the gut and that Gsdmc-mediated pyroptosis may provide a conduit for the release of antiparasitic factors from enterocytes to facilitate the clearance of worms. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Gasdermin; Helminth; IL-4/IL-13; Pyroptosis; Type 2 immunity
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238852
作者单位	State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China; Monell Chemical Senses Center, Philadelphia, PA 19104, United States; NODAI Genome Research Center, Tokyo University of Agriculture, Tokyo, 156-8502, Japan; US Department of Agriculture, Agricultural Research Service, Diet, Genomics and Immunology Laboratory, Beltsville Human Nutrition Research Center, Beltsville, MD 20705, United States; Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, 156-8502, Japan
推荐引用方式 GB/T 7714	Xi R.,Montague J.,Lin X.,et al. Up-regulation of gasdermin C in mouse small intestine is associated with lytic cell death in enterocytes in worm-induced type 2 immunity[J],2021,118(30).
APA	Xi R..,Montague J..,Lin X..,Lu C..,Lei W..,...&Jiang P..(2021).Up-regulation of gasdermin C in mouse small intestine is associated with lytic cell death in enterocytes in worm-induced type 2 immunity.Proceedings of the National Academy of Sciences of the United States of America,118(30).
MLA	Xi R.,et al."Up-regulation of gasdermin C in mouse small intestine is associated with lytic cell death in enterocytes in worm-induced type 2 immunity".Proceedings of the National Academy of Sciences of the United States of America 118.30(2021).