| MicroRNA-148/152 impair innate response and antigen presentation of TLR-triggered dendritic cells by targeting CaMKIIα. | |
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MedLine Citation:
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PMID: 21068402 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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MicroRNAs (miRNAs) are involved in the regulation of immunity, including the lymphocyte development and differentiation, and inflammatory cytokine production. Dendritic cells (DCs) play important roles in linking innate and adaptive immune responses. However, few miRNAs have been found to regulate the innate response and APC function of DCs to date. Calcium/calmodulin-dependent protein kinase II (CaMKII), a major downstream effector of calcium (Ca(2+)), has been shown to be an important regulator of the maturation and function of DCs. Our previous study showed that CaMKIIα could promote TLR-triggered production of proinflammatory cytokines and type I IFN. Inspired by the observations that dicer mutant Drosophila display defect in endogenous miRNA generation and higher CaMKII expression, we wondered whether miRNAs can regulate the innate response and APC function of DCs by targeting CaMKIIα. By predicting with software and confirming with functional experiments, we demonstrate that three members of the miRNA (miR)-148 family, miR-148a, miR-148b, and miR-152, are negative regulators of the innate response and Ag-presenting capacity of DCs. miR-148/152 expression was upregulated, whereas CaMKIIα expression was downregulated in DCs on maturation and activation induced by TLR3, TLR4, and TLR9 agonists. We showed that miR-148/152 in turn inhibited the production of cytokines including IL-12, IL-6, TNF-α, and IFN-β upregulation of MHC class II expression and DC-initiated Ag-specific T cell proliferation by targeting CaMKIIα. Therefore, miRNA-148/152 can act as fine-tuner in regulating the innate response and Ag-presenting capacity of DCs, which may contribute to the immune homeostasis and immune regulation. |
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Authors:
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Xingguang Liu; Zhenzhen Zhan; Li Xu; Feng Ma; Dong Li; Zhenhong Guo; Nan Li; Xuetao Cao |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-10 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-03 Completed Date: 2011-01-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 7244-51 Citation Subset: AIM; IM |
Affiliation:
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National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium-Calmodulin-Dependent Protein Kinase Type 2 / biosynthesis, immunology* Cytokines / immunology, metabolism Dendritic Cells / cytology, immunology*, metabolism Drosophila melanogaster Gene Expression Regulation / immunology* Immunity, Innate / physiology* Mice MicroRNAs / biosynthesis, immunology* Toll-Like Receptors / immunology, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/MIRN152 microRNA, mouse; 0/MicroRNAs; 0/Mirn148 microRNA, mouse; 0/Toll-Like Receptors; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinase Type 2 |
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