Dataset Information

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

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 CD56(dim) NK population in response to activation. PRDM1 coordinately suppresses the release of IFN-?, TNF-?, and TNF-? through direct binding to multiple conserved regulatory regions. Ablation of PRDM1 expression leads to enhanced production of IFN-? and TNF-? 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.

SUBMITTER: Smith MA

PROVIDER: S-EPMC3864810 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Smith Matthew A MA Maurin Michelle M Cho Hyun Il HI Becknell Brian B Freud Aharon G AG Yu Jianhua J Wei Sheng S Djeu Julie J Celis Esteban E Caligiuri Michael A MA Wright Kenneth L KL

Journal of immunology (Baltimore, Md. : 1950) 20101013 10

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 CD56(dim) NK popul ...[more]

PMID: 20944005

Similar Datasets

Project description:IntroductionThe different distribution of T cells among activation/differentiation stages in immune disorders may condition the outcome of mesenchymal stromal cell (MSC)-based therapies. Indeed, the effect of MSCs in the different functional compartments of T cells is not completely elucidated.MethodsWe investigated the effect of human bone marrow MSCs on naturally occurring peripheral blood functional compartments of CD4(+) and CD8(+) T cells: naive, central memory, effector memory, and effector compartments. For that, mononuclear cells (MNCs) stimulated with phorbol myristate acetate (PMA) plus ionomycin were cultured in the absence/presence of MSCs. The percentage of cells expressing tumor necrosis factor-alpha (TNF-?), interferon gamma (IFN?), and interleukin-2 (IL-2), IL-17, IL-9, and IL-6 and the amount of cytokine produced were assessed by flow cytometry. mRNA levels of IL-4, IL-10, transforming growth factor-beta (TGF-?), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) in purified CD4(+) and CD8(+) T cells, and phenotypic and mRNA expression changes induced by PMA?+?ionomycin stimulation in MSCs, were also evaluated.ResultsMSCs induced the reduction of the percentage of CD4(+) and CD8(+) T cells producing TNF-?, IFN?, and IL-2 in all functional compartments, except for naive IFN?(+)CD4(+) T cells. This inhibitory effect differentially affected CD4(+) and CD8(+) T cells as well as the T-cell functional compartments; remarkably, different cytokines showed distinct patterns of inhibition regarding both the percentage of producing cells and the amount of cytokine produced. Likewise, the percentages of IL-17(+), IL-17(+)TNF-?(+), and IL-9(+) within CD4(+) and CD8(+) T cells and of IL-6(+)CD4(+) T cells were decreased in MNC-MSC co-cultures. MSCs decreased IL-10 and increased IL-4 mRNA expression in stimulated CD4(+) and CD8(+) T cells, whereas TGF-? was reduced in CD8(+) and augmented in CD4(+) T cells, with no changes for CTLA4. Finally, PMA?+?ionomycin stimulation did not induce significant alterations on MSCs phenotype but did increase indoleamine-2,3-dioxygenase (IDO), inducible costimulatory ligand (ICOSL), IL-1?, IL-8, and TNF-? mRNA expression.ConclusionsOverall, our study showed that MSCs differentially regulate the functional compartments of CD4(+) and CD8(+) T cells, which may differentially impact their therapeutic effect in immune disorders. Furthermore, the influence of MSCs on IL-9 expression can open new possibilities for MSC-based therapy in allergic diseases.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets