Juárez Martín-Delgado, IgnacioShi, SuHerbert, Zachary T.John R. TeijaroMoulton, Vaishali R.2024-01-312024-01-312022-09-16Juarez I, Su S, Herbert ZT, Teijaro JR, Moulton VR. Splicing factor SRSF1 is essential for CD8 T cell function and host antigen-specific viral immunity. Front Immunol. 2022 Sep 16;13:906355. doi: 10.3389/fimmu.2022.9063551664-322410.3389/fimmu.2022.906355https://hdl.handle.net/20.500.14352/97192Cytotoxic CD8 T cells are crucial for the host antigen-specific immune response to viral pathogens. Here we report the identification of an essential role for the serine/arginine-rich splicing factor (SRSF) 1 in CD8 T cell homeostasis and function. Specifically, SRSF1 is necessary for the maintenance of normal CD8 T lymphocyte numbers in the lymphoid compartment, and for the proliferative capacity and cytotoxic function of CD8 T cells. Furthermore, SRSF1 is required for antigen-specific IFN-γ cytokine responses in a viral infection challenge in mice. Transcriptomics analyses of Srsf1-deficient T cells reveal that SRSF1 controls proliferation, MAP kinase signaling and IFN signaling pathways. Mechanistically, SRSF1 controls the expression and activity of the Mnk2/p38-MAPK axis at the molecular level. Our findings reveal previously unrecognized roles for SRSF1 in the physiology and function of cytotoxic CD8 T lymphocytes and a potential molecular mechanism in viral immunopathogenesis.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal articlehttps://www.frontiersin.org/articles/10.3389/fimmu.2022.906355/fullhttps://pubmed.ncbi.nlm.nih.gov/36189299/open access612.017SRSF1T cellsCytokinesImmune responseViral infectionInmunología2412 Inmunología