Glutathione S-transferase theta 1 protects against colitis through goblet cell differentiation via interleukin-22

Jae Hyeon Kim, Jae Bum Ahn, Da Hye Kim, Soochan Kim, Hyun Woo Ma, Xiumei Che, Dong Hyuk Seo, Tae Il Kim, Won Ho Kim, Jae Hee Cheon, Seung Won Kim

Research output: Contribution to journalArticle

Abstract

The enzyme glutathione S-transferase theta 1 (GSTT1) is involved in detoxifying chemicals, including reactive oxygen species (ROS). Here, we provide a significant insight into the role of GSTT1 in inflammatory bowel disease (IBD). We identified decreased expression of GSTT1 in inflamed colons from IBD patients compared to controls. We intrarectally or intraperitoneally delivered Gstt1 gene to mice with dextran sodium sulfate (DSS)-induced colitis and noted attenuation of colitis through gene transfer of Gstt1 via an IL-22 dependent pathway. Downregulation of GSTT1 by pathogen-associated molecular patterns (PAMPs) of microbes reduced innate defense responses and goblet cell differentiation. The GSTT1 mutation in intestinal epithelial cells (IECs) and IBD patients decreased its dimerization, which was connected to insufficient phosphorylation of signal transducer and activator of transcription-3 and p38/mitogen-activated protein kinase by their common activator, IL-22. GSTT1 ameliorated colitis and contributed as a modulator of goblet cells through sensing pathogens and host immune responses. Its mutations are linked to chronic intestinal inflammation due to its insufficient dimerization. Our results provide new insights into GSTT1 mutations that are linked to chronic intestinal inflammation due to its insufficient dimerization and their functional consequences in IBDs.

Original languageEnglish
Pages (from-to)3289-3304
Number of pages16
JournalFASEB Journal
Volume34
Issue number2
DOIs
Publication statusPublished - 2020 Feb 1

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Kim, J. H., Ahn, J. B., Kim, D. H., Kim, S., Ma, H. W., Che, X., Seo, D. H., Kim, T. I., Kim, W. H., Cheon, J. H., & Kim, S. W. (2020). Glutathione S-transferase theta 1 protects against colitis through goblet cell differentiation via interleukin-22. FASEB Journal, 34(2), 3289-3304. https://doi.org/10.1096/fj.201902421R