| Literature DB >> 35385697 |
Ming Zhao1, Kaiqun Ren2, Xiwen Xiong3, Yue Xin3, Yujie Zou4, Jason C Maynard5, Angela Kim1, Alexander P Battist1, Navya Koneripalli1, Yusu Wang4, Qianyue Chen4, Ruyue Xin4, Chenyan Yang3, Rong Huang3, Jiahui Yu3, Zan Huang1, Zengdi Zhang1, Haiguang Wang1, Daoyuan Wang6, Yihui Xiao6, Oscar C Salgado7, Nicholas N Jarjour7, Kristin A Hogquist8, Xavier S Revelo9, Alma L Burlingame5, Xiang Gao4, Jakob von Moltke10, Zhaoyu Lin11, Hai-Bin Ruan12.
Abstract
The epithelium is an integral component of mucosal barrier and host immunity. Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. However, it is unknown how helminth infection and the resulting cytokine milieu drive epithelial remodeling and orchestrate alarmin secretion. Here, we report that epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification was induced upon helminth infections. By modifying and activating the transcription factor STAT6, O-GlcNAc transferase promoted the transcription of lineage-defining Pou2f3 in tuft cell differentiation and IL-25 production. Meanwhile, STAT6 O-GlcNAcylation activated the expression of Gsdmc family genes. The membrane pore formed by GSDMC facilitated the unconventional secretion of IL-33. GSDMC-mediated IL-33 secretion was indispensable for effective anti-helminth immunity and contributed to induced intestinal inflammation. Protein O-GlcNAcylation can be harnessed for future treatment of type 2 inflammation-associated human diseases.Entities:
Keywords: Gasdermin; IL-10; IL-25; IL-33; O-GlcNAc; OGT; STAT6; Tuft cell; colitis; goblet cell
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Year: 2022 PMID： 35385697 PMCID： PMC9109499 DOI： 10.1016/j.immuni.2022.03.009
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 43.474