Control of nutrient uptake by IRF4 orchestrates innate immune memory.

Autor: Santosa EK; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY, USA., Kim H; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Rückert T; Innate Immunity, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Leibniz Institut, Berlin, Germany., Le Luduec JB; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Abbasi AJ; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Wingert CK; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Peters L; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Frost JN; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Hsu KC; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Romagnani C; Innate Immunity, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Leibniz Institut, Berlin, Germany.; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany.; Leibniz-Science Campus Chronic Inflammation, Berlin, Germany., Sun JC; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. sunj@mskcc.org.; Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY, USA. sunj@mskcc.org.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2023 Oct; Vol. 24 (10), pp. 1685-1697. Date of Electronic Publication: 2023 Sep 11.
DOI: 10.1038/s41590-023-01620-z
Abstrakt: Natural killer (NK) cells are innate cytotoxic lymphocytes with adaptive immune features, including antigen specificity, clonal expansion and memory. As such, NK cells share many transcriptional and epigenetic programs with their adaptive CD8 + T cell siblings. Various signals ranging from antigen, co-stimulation and proinflammatory cytokines are required for optimal NK cell responses in mice and humans during virus infection; however, the integration of these signals remains unclear. In this study, we identified that the transcription factor IRF4 integrates signals to coordinate the NK cell response during mouse cytomegalovirus infection. Loss of IRF4 was detrimental to the expansion and differentiation of virus-specific NK cells. This defect was partially attributed to the inability of IRF4-deficient NK cells to uptake nutrients required for survival and memory generation. Altogether, these data suggest that IRF4 is a signal integrator that acts as a secondary metabolic checkpoint to orchestrate the adaptive response of NK cells during viral infection.
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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