{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:27:07Z","timestamp":1777652827332,"version":"3.51.4"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:p>Autoimmune hepatitis (AIH) is an inflammatory liver disease driven by the hyperactivation of various intrahepatic antigen\u2010specific T cells due to a breach of immune tolerance. Studies in immunometabolism demonstrate that activated T cells harbor increased levels of reactive oxygen species that cause oxidative DNA damage. In this study, we assessed the potential of DNA damage repair enzyme MutT homolog 1 (MTH1) as a therapeutic target in AIH and karonudib as a novel drug for patients with AIH. We report herein that MTH1 expression was significantly increased in liver samples from patients with AIH compared to patients with chronic hepatitis B and nonalcoholic fatty liver disease and from healthy controls. In addition, the expression of MTH1 was positively correlated with AIH disease severity. We further found abundant T cells that expressed MTH1 in AIH. Next, we found that karonudib significantly altered T\u2010cell receptor signaling in human T cells and robustly inhibited proliferation of human T cells <jats:italic toggle=\"yes\">in vitro<\/jats:italic>. Interestingly, our data reflected a preferential inhibition of DNA damage repair in activated T cells by karonudib. Moreover, MTH1 was required to develop liver inflammation and damage because specific deletion\u00a0of MTH1 in T cells ameliorated liver injury\u00a0in the concanavalin A (Con A)\u2010induced hepatitis model\u00a0by inhibiting T\u2010cell activation and proliferation. Lastly, we validated the protective effect of karonudib on the Con A\u2010induced hepatitis model. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> MTH1 functions as a critical regulator in the development of AIH, and its inhibition in activated T cells reduces liver inflammation and damage.<\/jats:p>","DOI":"10.1002\/hep4.1862","type":"journal-article","created":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T05:49:15Z","timestamp":1639201755000},"page":"1016-1031","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":8,"title":["MutT Homolog 1 Inhibitor Karonudib Attenuates Autoimmune Hepatitis by Inhibiting DNA Repair in Activated T Cells"],"prefix":"10.1097","volume":"6","author":[{"given":"Yong","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangwei","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Thyroid Breast 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