Divergent Role for STAT5 in the Adaptive Responses of Natural Killer Cells
Gabriela M. Wiedemann,
Simon Grassmann,
Colleen M. Lau,
Moritz Rapp,
Alejandro V. Villarino,
Christin Friedrich,
Georg Gasteiger,
John J. O’Shea,
Joseph C. Sun
Affiliations
Gabriela M. Wiedemann
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Internal Medicine II, Technical University of Munich, Munich, Germany
Simon Grassmann
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Colleen M. Lau
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Moritz Rapp
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Alejandro V. Villarino
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
Christin Friedrich
Würzburg Institute of Systems Immunology, Julius-Maximilians-Universität, 97078 Würzburg, Germany
Georg Gasteiger
Würzburg Institute of Systems Immunology, Julius-Maximilians-Universität, 97078 Würzburg, Germany
John J. O’Shea
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
Joseph C. Sun
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY 10065, USA; Corresponding author
Summary: Natural killer (NK) cells are innate lymphocytes with the capacity to elicit adaptive features, including clonal expansion and immunological memory. Because signal transducer and activator of transcription 5 (STAT5) is essential for NK cell development, the roles of this transcription factor and its upstream cytokines interleukin-2 (IL-2) and IL-15 during infection have not been carefully investigated. In this study, we investigate how STAT5 regulates transcription during viral infection. We demonstrate that STAT5 is induced in NK cells by IL-12 and STAT4 early after infection and that partial STAT5 deficiency results in a defective capacity of NK cells to generate long-lived memory cells. Furthermore, we find a functional dichotomy of IL-2 and IL-15 signaling outputs during viral infection, whereby both cytokines drive clonal expansion, but only IL-15 is required for memory NK cell survival. We thus highlight a role for STAT5 signaling in promoting an optimal anti-viral NK cell response.
