{"entity": "publication", "iuid": "fd738e4f8a3840b1820a97c8deebf787", "timestamp": "2026-08-20T21:26:08.113Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/fd738e4f8a3840b1820a97c8deebf787.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/fd738e4f8a3840b1820a97c8deebf787"}}, "title": "MutT Homolog 1 Inhibitor Karonudib Attenuates Autoimmune Hepatitis by Inhibiting DNA Repair in Activated T Cells.", "authors": [{"family": "Chen", "given": "Yong", "initials": "Y"}, {"family": "Hua", "given": "Xiangwei", "initials": "X"}, {"family": "Huang", "given": "Bingyuan", "initials": "B"}, {"family": "Karsten", "given": "Stella", "initials": "S", "orcid": "0000-0001-6191-4314", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3a27ec21e4a34600aa24a7213372e19c.json"}}, {"family": "You", "given": "Zhengrui", "initials": "Z"}, {"family": "Li", "given": "Bo", "initials": "B"}, {"family": "Li", "given": "You", "initials": "Y"}, {"family": "Li", "given": "Yikang", "initials": "Y"}, {"family": "Liang", "given": "Jubo", "initials": "J"}, {"family": "Zhang", "given": "Jun", "initials": "J"}, {"family": "Wei", "given": "Yiran", "initials": "Y"}, {"family": "Chen", "given": "Ruiling", "initials": "R"}, {"family": "Lyu", "given": "Zhuwan", "initials": "Z", "orcid": "0000-0002-8437-8777", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/107db31746bf48cda42890aa3ef7b6ee.json"}}, {"family": "Xiao", "given": "Xiao", "initials": "X"}, {"family": "Lian", "given": "Min", "initials": "M"}, {"family": "Wei", "given": "Jue", "initials": "J"}, {"family": "Fang", "given": "Jingyuan", "initials": "J"}, {"family": "Miao", "given": "Qi", "initials": "Q"}, {"family": "Wang", "given": "Qixia", "initials": "Q"}, {"family": "Berglung", "given": "Ulrika Warpman", "initials": "UW"}, {"family": "Tang", "given": "Ruqi", "initials": "R"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Ma", "given": "Xiong", "initials": "X", "orcid": "0000-0001-9616-4672", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b13d1a5dd21946fba0cbc41923315f01.json"}}], "type": "journal article", "published": "2022-05-00", "journal": {"title": "Hepatol Commun", "issn": "2471-254X", "volume": "6", "issue": "5", "pages": "1016-1031", "issn-l": null}, "abstract": "Autoimmune hepatitis (AIH) is an inflammatory liver disease driven by the hyperactivation of various intrahepatic antigen-specific 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-cell receptor signaling in human T cells and robustly inhibited proliferation of human T cells in vitro. 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 of MTH1 in T cells ameliorated liver injury in the concanavalin A (Con A)-induced hepatitis model by inhibiting T-cell activation and proliferation. Lastly, we validated the protective effect of karonudib on the Con A-induced hepatitis model. Conclusion: MTH1 functions as a critical regulator in the development of AIH, and its inhibition in activated T cells reduces liver inflammation and damage.", "doi": "10.1002/hep4.1862", "pmid": "34894107", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9035570"}, {"db": "pii", "key": "02009842-202205000-00008"}], "notes": [], "created": "2026-08-20T06:33:04.642Z", "modified": "2026-08-20T06:33:04.817Z"}