Up-regulation of gasdermin C in mouse small intestine is associated with lytic cell death in enterocytes in worm-induced type 2 immunity
Ranhui Xi, Julia Montague, Xiaoli Lin, Chanyi Lu, Weiwei Lei, Keisuke Tanaka, Yali V. Zhang, Xin Xu, Xin Zheng, Xuedong Zhou, Joseph F. Urban, Ken Iwatsuki, Robert F. Margolskee, Ichiro Matsumoto, Marco Tizzano, Jiyao Li, Peihua Jiang
Abstract
Significance Despite improved understanding of cellular and molecular events mediating type 2 immune responses in the gut, how these changes facilitate worm expulsion remains largely unknown. We identified pyroptosis-effector gasdermin C genes ( Gsdmc s) as type 2 cytokine-regulated target genes in intestinal epithelial cells. Furthermore, we showed that overexpression of Gsdmc2 triggered pyroptosis. Organoid cultures and in vivo mouse models were used to show that activating type 2 immunity leads to lytic cell death in gut epithelium and cleavage of Gsdmcs. We thus revealed a role of gasdermin-mediated lytic cell death in worm-induced type 2 immunity. Parasitic infection often leads to malnutrition and retarded growth; since this may involve villus atrophy, gasdermin activity may provide a pharmaceutical target for treatment.