The transcription factor Zbtb32 controls the proliferative burst of virus-specific natural killer cells responding to infection

Nat Immunol. 2014 Jun;15(6):546-53. doi: 10.1038/ni.2876. Epub 2014 Apr 20.


Natural killer (NK) cells are innate lymphocytes that exhibit many features of adaptive immunity, including clonal proliferation and long-lived memory. Here we demonstrate that the BTB-ZF transcription factor Zbtb32 (also known as ROG, FAZF, TZFP and PLZP) was essential for the proliferative burst and protective capacity of virus-specific NK cells. Signals from proinflammatory cytokines were both necessary and sufficient to induce high expression of Zbtb32 in NK cells. Zbtb32 facilitated NK cell proliferation during infection by antagonizing the anti-proliferative factor Blimp-1 (Prdm1). Our data support a model in which Zbtb32 acts as a cellular 'hub' through which proinflammatory signals instruct a 'proliferation-permissive' state in NK cells, thereby allowing their prolific expansion in response to viral infection.

Publication types

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

MeSH terms

  • Adaptive Immunity
  • Animals
  • Cell Proliferation
  • Cell Survival / immunology
  • Cytokines / immunology
  • Herpesviridae Infections / immunology*
  • Immunologic Memory
  • Inflammation / immunology
  • Inflammation / virology
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muromegalovirus / immunology
  • Positive Regulatory Domain I-Binding Factor 1
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology*
  • Transcription Factors / antagonists & inhibitors


  • Cytokines
  • Prdm1 protein, mouse
  • Repressor Proteins
  • Rog protein, mouse
  • Transcription Factors
  • Positive Regulatory Domain I-Binding Factor 1

Associated data

  • GEO/GSE15907