{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T06:14:27Z","timestamp":1774332867468,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Clinician Scientist Program of the University Medicine Essen Clinician Scientist Academy (UMEA)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Ubiquitin-specific peptidase 22 (Usp22) cleaves ubiquitin moieties from numerous proteins, including histone H2B and transcription factors. Recently, it was reported that Usp22 acts as a negative regulator of interferon-dependent responses. In the current study, we investigated the role of Usp22 deficiency in acute viral infection with lymphocytic choriomeningitis virus (LCMV). We found that the lack of Usp22 on bone marrow-derived cells (Usp22fl\/fl Vav1-Cre mice) reduced the induction of type I and II interferons. A limited type I interferon response did not influence virus replication. However, restricted expression of PD-L1 led to increased frequencies of functional virus-specific CD8+ T cells and rapid death of Usp22-deficient mice. CD8+ T cell depletion experiments revealed that accelerated CD8+ T cells were responsible for enhanced lethality in Usp22 deficient mice. In conclusion, we found that the lack of Usp22 generated a pathological CD8+ T cell response, which gave rise to severe disease in mice.<\/jats:p>","DOI":"10.3390\/vaccines11101563","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T03:05:19Z","timestamp":1696475119000},"page":"1563","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Usp22 Deficiency Leads to Downregulation of PD-L1 and Pathological Activation of CD8+ T Cells and Causes Immunopathology in Response to Acute LCMV Infection"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6747-1240","authenticated-orcid":false,"given":"Justa","family":"Friebus-Kardash","sequence":"first","affiliation":[{"name":"Institute of Immunology, Medical Faculty, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"Department of Nephrology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa Charlotte","family":"Christ","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Medical Faculty, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolaus","family":"Dietlein","sequence":"additional","affiliation":[{"name":"Division of Cellular Immunology, German Cancer Research Center, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1441-5460","authenticated-orcid":false,"given":"Abdelrahman","family":"Elwy","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Medical Faculty, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hossam","family":"Abdelrahman","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Medical Faculty, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Holnsteiner","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Medical Faculty, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongwen","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Medical Faculty, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Reimer","family":"Rodewald","sequence":"additional","affiliation":[{"name":"Division of Cellular Immunology, German Cancer Research Center, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl Sebastian","family":"Lang","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Medical Faculty, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nri1573","article-title":"Immunology of hepatitis B virus and hepatitis C virus infection","volume":"5","author":"Rehermann","year":"2005","journal-title":"Nat. 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