Document Detail


Regulation of dendritic cell activation by microRNA let-7c and BLIMP1.
MedLine Citation:
PMID:  23298838     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mice with a DC-specific deletion of the transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp1) exhibit a lupus-like phenotype, secondary to enhanced DC production of IL-6. Here we explored further phenotypic changes in Blimp1-deficient DCs, the molecular mechanism underlying these changes, and their relevance to human disease. Blimp1-deficient DCs exhibited elevated expression of MHC II, and exposure to TLR agonists increased secretion of proinflammatory cytokines. This phenotype reflects enhanced expression of the microRNA let-7c, which is regulated by BLIMP1. Let-7c reciprocally inhibited Blimp1 and also blocked LPS-induced suppressor of cytokine signaling-1 (SOCS1) expression, contributing to the proinflammatory phenotype of Blimp1-deficient DCs. DCs from Blimp1 SLE-risk allele carriers exhibited analogous phenotypic changes, including decreased BLIMP1 expression, increased let-7c expression, and increased expression of proinflammatory cytokines. These results suggest that let-7c regulates DC phenotype and confirm the importance of BLIMP1 in maintaining tolerogenic DCs in both mice and humans.
Authors:
Sun Jung Kim; Peter K Gregersen; Betty Diamond
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-09
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  123     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-04-19     Completed Date:  2013-05-13     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  823-33     Citation Subset:  AIM; IM    
Affiliation:
Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research (FIMR), Manhasset, New York, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Cytokines / metabolism
Dendritic Cells / immunology*,  metabolism*
Female
Gene Expression
Humans
Lupus Erythematosus, Systemic / etiology,  genetics,  immunology
Mice
Mice, Knockout
MicroRNAs / genetics*,  metabolism*
Middle Aged
Models, Immunological
Molecular Sequence Data
Phenotype
Repressor Proteins / genetics,  immunology
Signal Transduction
Suppressor of Cytokine Signaling Proteins / genetics
Transcription Factors / deficiency,  genetics,  immunology*
Grant Support
ID/Acronym/Agency:
K01 AR059378/AR/NIAMS NIH HHS; K01AR059378/AR/NIAMS NIH HHS; RC2AR059092/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 0/MicroRNAs; 0/Prdm1 protein, mouse; 0/Repressor Proteins; 0/Socs1 protein, mouse; 0/Suppressor of Cytokine Signaling Proteins; 0/Transcription Factors; 0/mirnlet7 microRNA, mouse; 138415-26-6/PRDM1 protein, human
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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