PRDM1/Blimp-1 controls effector cytokine production in human NK cells

Matthew A. Smith, Michelle Maurin, Hyun Il Cho, Brian Becknell, Aharon G. Freud, Jianhua Yu, Sheng Wei, Julie Djeu, Esteban Celis, Michael A. Caligiuri, Kenneth L. Wright

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48 Scopus citations

Abstract

NK cells are major effectors of the innate immune response through cytolysis and bridge to the adaptive immune response through cytokine release. The mediators of activation are well studied; however, little is known about the mechanisms that restrain activation. In this report, we demonstrate that the transcriptional repressor PRDM1 (also known as Blimp-1 or PRDI-BF1) is a critical negative regulator of NK function. Three distinct PRDM1 isoforms are selectively induced in the CD56dim NK population in response to activation. PRDM1 coordinately suppresses the release of IFN-γ, TNF-α, and TNF-β through direct binding to multiple conserved regulatory regions. Ablation of PRDM1 expression leads to enhanced production of IFN-γ and TNF-α but does not alter cytotoxicity, whereas overexpression blocks cytokine production. PRDM1 response elements are defined at the IFNG and TNF loci. Collectively, these data demonstrate a key role for PRDM1 in the negative regulation of NK activation and position PRDM1 as a common regulator of the adaptive and innate immune response.

Original languageEnglish (US)
Pages (from-to)6058-6067
Number of pages10
JournalJournal of Immunology
Volume185
Issue number10
DOIs
Publication statusPublished - Nov 15 2010
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Smith, M. A., Maurin, M., Cho, H. I., Becknell, B., Freud, A. G., Yu, J., ... Wright, K. L. (2010). PRDM1/Blimp-1 controls effector cytokine production in human NK cells. Journal of Immunology, 185(10), 6058-6067. https://doi.org/10.4049/jimmunol.1001682