Usp22 Deficiency Switches Antiviral Response into Pathological CD8+ T Cell Activation via Downregulation of PD-L1

• DOI: 10.20944/preprints202308.0878.v1
• Publication Date: 2023-08-14T00:31:10Z
• Authors: Justa Friebus-Kar...; Theresa Charlotte...; Nikolaus Dietlein; Abdelrahman Elwy; Hossam Abdelrahman; Lisa Holnsteiner; Zhongwen Hu; Hans-Reimer Rodew...; Karl Sebastian Lang

Ubiquitin-Specific-peptidase 22 (Usp22) cleaves ubiquitin moieties from numerous proteins, in particular transcription factors. Recently, it was reported that Usp22 acts as negative regulator of interferon-dependent responses. In the current study, we investigated role deficiency upon acute viral infection with lymphocytic choriomeningitis (LCMV) virus. We found lack on bone marrow derived cells (Usp22 fl/fl Vav1-Cre mice) reduced induction type I and II interferons. Limited interferon response did not influence virus replication. However, restricted expression PD-L1 led to increased frequencies functional virus-specific CD8+ T rapid death deficient mice. cell depletion experiments revealed accelerated were responsible for enhanced lethality conclusion, generated a pathological response, which gave rise severe disease