Splicing factor SRSF1 is essential for CD8 T cell function and host antigen-specific viral immunity.

Autor:	Juarez I; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.; Department of Immunology, Ophthalmology and ENT, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain., Su S; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.; Cardiovascular Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States., Herbert ZT; Molecular Biology Core Facilities at Dana-Farber Cancer Institute, Boston, MA, United States., Teijaro JR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States., Moulton VR; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Sep 16; Vol. 13, pp. 906355. Date of Electronic Publication: 2022 Sep 16 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.906355
Abstrakt:	Cytotoxic 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Juarez, Su, Herbert, Teijaro and Moulton.)
Databáze:	MEDLINE
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