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PMID: 20944005 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 185 ·No. 10 ·2010-11-15 ·Pages 6058-67

Smith MA, Maurin M, Cho HI, Becknell B, Freud AG, Yu J, Wei S, Djeu J, Celis E, Caligiuri MA, Wright KL

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-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.

MeSH Terms
Animals Blotting, Western Chromatin Immunoprecipitation Cytokines/biosynthesis Enzyme-Linked Immunosorbent Assay Gene Expression Regulation/immunology Humans Killer Cells, Natural/immunology,metabolism Lymphocyte Activation/immunology Mice Mice, Inbred C57BL Oligonucleotide Array Sequence Analysis Positive Regulatory Domain I-Binding Factor 1 Repressor Proteins/immunology,metabolism Reverse Transcriptase Polymerase Chain Reaction
Chemicals
Cytokines Repressor Proteins PRDM1 protein, human Positive Regulatory Domain I-Binding Factor 1
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Smith Matthew A
H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612, USA.
Maurin Michelle
Cho Hyun Il
Becknell Brian
Freud Aharon G
Yu Jianhua
Wei Sheng
Djeu Julie
Celis Esteban
Caligiuri Michael A
Wright Kenneth L
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Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
1550-6606
DOI
10.4049/jimmunol.1001682
Published
2010-11-15
Epub
2010-00-13
Pages
6058-67
Language
English
Region
United States
NLM ID
2985117R
PMCID
PMC3864810
Subset
IM
Grants
NCI NIH HHS · R01 CA114504 · United States
External Links
PubMed source DOI: 10.4049/jimmunol.1001682 PMC Full Text View journal details
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