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However, the precise regulatory mechanism of OTUD6A remains unclear. In this study, we found that OTUD6A significantly inhibited the production of type I interferon. Consistently, peritoneal macrophages and bone marrow-derived macrophages from Otud6a\u2212\/\u2212 mice produced more type I interferon after virus infection compared to cells from WT mice. Otud6a\u2212\/\u2212\u2212 mice also exhibited increased resistance to lethal HSV-1 and VSV infections, as well as LPS attacks due to decreased inflammatory responses. Mechanistically, mass spectrometry results revealed that UBC13 was an OTUD6A-interacting protein, and the interaction was significantly enhanced after HSV-1 stimulation. Taken together, our findings suggest that OTUD6A plays a crucial role in the innate immune response and may serve as a potential therapeutic target for infectious disease.<\/jats:p>","DOI":"10.3390\/v15081761","type":"journal-article","created":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T10:14:38Z","timestamp":1692353678000},"page":"1761","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Deubiquitinase OTUD6A Regulates Innate Immune Response via Targeting UBC13"],"prefix":"10.3390","volume":"15","author":[{"given":"Zhiwei","family":"Li","sequence":"first","affiliation":[{"name":"College of Life Sciences, Hebei University, Baoding 071002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanwen","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Sciences, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Systems Biomedicine, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Systems Biomedicine, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Hebei University, Baoding 071002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Hebei University, Baoding 071002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Hebei University, Baoding 071002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengde","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing 100142, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Hebei University, Baoding 071002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7444-729X","authenticated-orcid":false,"given":"Fuping","family":"You","sequence":"additional","affiliation":[{"name":"Department of Systems Biomedicine, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"publisher","first-page":"25208","DOI":"10.1038\/srep25208","article-title":"Exposure to Melan-A\/MART-126-35 tumor epitope specific CD8(+)T cells reveals immune escape by affecting the ubiquitin-proteasome system (UPS)","volume":"6","author":"Ebstein","year":"2016","journal-title":"Sci. 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