Mahesh Kathania, Desh Raj, Thirupugal Govindarajan, Dinesh Ravindra Raju, Amit K Verma, Anirban Roy, Risha Mathur, Jenna Woody, Amir Kumar Singh, Chul Ahn, Suraj Patel, Jianyi Yin, Andrew Lemoff, Arianne L Theiss, Chao Xing, Tuoqi Wu, Ezra Burstein, K Venuprasad
{"title":"Zbtb44-mediated transcriptional repression critically regulates colonic inflammation.","authors":"Mahesh Kathania, Desh Raj, Thirupugal Govindarajan, Dinesh Ravindra Raju, Amit K Verma, Anirban Roy, Risha Mathur, Jenna Woody, Amir Kumar Singh, Chul Ahn, Suraj Patel, Jianyi Yin, Andrew Lemoff, Arianne L Theiss, Chao Xing, Tuoqi Wu, Ezra Burstein, K Venuprasad","doi":"10.1038/s41590-026-02675-4","DOIUrl":null,"url":null,"abstract":"<p><p>The regulatory mechanisms that maintain colonic immune homeostasis remain incompletely understood. Here we show that genetic deletion of Zbtb44, a previously uncharacterized member of the ZBTB transcription factor family, leads to spontaneous colitis and rectal prolapse. Zbtb44<sup>-/-</sup> T cells expressed increased IFN-γ, a pro-inflammatory cytokine strongly associated with human inflammatory bowel disease. Mechanistically, Zbtb44 undergoes SUMOylation, which facilitates its interaction with a conserved SUMO-interacting motif in T-bet, enabling binding to the IFN-γ promoter and enhancer to restrain chronic IFN-γ production. Together, these findings demonstrate that Zbtb44 is a key regulator of colonic inflammation, a role that could be exploited therapeutically.</p>","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":"2215-2224"},"PeriodicalIF":26.5000,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41590-026-02675-4","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/10/12 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The regulatory mechanisms that maintain colonic immune homeostasis remain incompletely understood. Here we show that genetic deletion of Zbtb44, a previously uncharacterized member of the ZBTB transcription factor family, leads to spontaneous colitis and rectal prolapse. Zbtb44-/- T cells expressed increased IFN-γ, a pro-inflammatory cytokine strongly associated with human inflammatory bowel disease. Mechanistically, Zbtb44 undergoes SUMOylation, which facilitates its interaction with a conserved SUMO-interacting motif in T-bet, enabling binding to the IFN-γ promoter and enhancer to restrain chronic IFN-γ production. Together, these findings demonstrate that Zbtb44 is a key regulator of colonic inflammation, a role that could be exploited therapeutically.
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Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.
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