Divergent Role for STAT5 in the Adaptive Responses of Natural Killer Cells

Cell Rep. 2020 Dec 15;33(11):108498. doi: 10.1016/j.celrep.2020.108498.


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.

Keywords: IL-15; IL-2; MCMV; NK cell; STAT5; clonal expansion; memory.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Humans
  • Killer Cells, Natural / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • STAT5 Transcription Factor / metabolism*
  • Signal Transduction


  • STAT5 Transcription Factor