Research ArticleNK CELLS

The transcription factor Bcl11b promotes both canonical and adaptive NK cell differentiation

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Science Immunology  12 Mar 2021:
Vol. 6, Issue 57, eabc9801
DOI: 10.1126/sciimmunol.abc9801

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Human NK cell circuitry

Natural killer (NK) cells are innate immune effector cells that undergo differentiation and education to facilitate protective responses during viral infection and cancer. Holmes et al. performed an integrated transcriptional and epigenetic profiling of human peripheral blood NK cell subsets to construct the transcription factor networks regulating their differentiation. NK cell differentiation converged along an axis that terminated in adaptive NK cells and was progressively regulated by the transcription factor Bcl11b. Ectopic expression of Bcl11b or loss of function in patients harboring BCL11B mutations altered NK cell maturation. Although Bcl11b is known to regulate T cell development, these results identify a complementary role in NK cell differentiation and provide insight into other transcription factors potentially involved in human NK cell identity. See related Focus by Rückert et al. in this issue.

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