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- W4313365819 abstract "Abstract Th17 cells producing cytokines, IL-17A and IL-22 are important key player in host defense. We have reported that intestinal epithelial expression of IL-17 receptors in gut epithelial cells control the development of microbiota. To study the roles of these receptors in response to an attaching and effacing pathogen we challenged Citobacter rodenium (C. rodentium) to intestinal epithelial specific IL-17RA or IL-22RA1 KO mice. Conditional deletion of Il17ra or Il22ra1 resulted in increased bacterial growth in the colon as well as enhanced dissemination to the spleen. It suggested both cytokine receptors are required for control of this infection. In addition this was supported by unbiased RNAseq analysis of the colonic epithelium that showed diminished expression of Pigr, Duox2 and Duoxa2 in the absence of IL-17RA signaling and reduced Bcl3 expression in the absence of IL-22ra1 expression. To elucidate whether production from epithelial cells effect bacteria killing we cultured crypt and stimulated IL-17A. It resulted in increasing Pigr, Duoxa2 and Duox2 were associated with increasing bacteria killing. Pigr binds dimeric IgA and translocation into lumen from lamina propria, while Duox2 and Duoxa2 make complex and produce hydrogen peroxide into lumen from apical epithelial cell membrane. These result suggested mucosal immunity to C. rodentium requires both IL-17RA and IL-22ra1 signaling and that IL-17RA regulates transcytosis of C. rodentium specific IgA as well as luminal hydrogen peroxide concentrations to control bacterial growth. In contrast, Il-22Ra1 regulates epithelial Bcl3 expression, which restrains TNFα and NF-κB signaling in the colonic epithelium." @default.
- W4313365819 created "2023-01-06" @default.
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- W4313365819 date "2019-05-01" @default.
- W4313365819 modified "2023-09-26" @default.
- W4313365819 title "IL-17 receptor and IL-22 receptor signaling in <i>Citrrobacter rodentium</i> infection" @default.
- W4313365819 doi "https://doi.org/10.4049/jimmunol.202.supp.192.1" @default.
- W4313365819 hasPublicationYear "2019" @default.
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