Research ArticleIMMUNOGENOMICS

Core-binding factor β and Runx transcription factors promote adaptive natural killer cell responses

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Science Immunology  08 Dec 2017:
Vol. 2, Issue 18, eaan3796
DOI: 10.1126/sciimmunol.aan3796

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Memory wiring in natural killer cells

Although clonal expansion and immune memory are associated with adaptive immunity, Ly49H-expressing natural killer (NK) cells undergo clonal proliferation in response to mouse cytomegalovirus (MCMV) infection and form long-lived memory cells. Previous studies have shown that interleukin-12, via activation of signal transducer and activator of transcription 4 (STAT4), drives expansion of MCMV-responsive NK cells. Here, by carrying out ChIP-seq to identify downstream targets of STAT4, Rapp et al. demonstrate that genes encoding transcription factors Runx1 and Runx3 are direct targets of STAT4. By further evaluating the ability of Runx1- and Runx3-deficient NK cells to respond to MCMV infection, they show that Runx1 and Runx3 play nonredundant roles in promoting clonal expansion of NK cells.