MicroRNA-223-3p modulates dendritic cell function and ameliorates experimental autoimmune myocarditis by targeting the NLRP3 inflammasome. (January 2020)

• Record Type: Journal Article
• Authors: Chen, Liangqi; Hou, Xinyu; Zhang, Maomao; Zheng, Yang; Zheng, Xianghui; Yang, Qingyuan; Li, Jing; Gu, Nan; Zhang, Min; Sun, Yong; Wu, Jian; Yu, Bo
• Is Part Of: Molecular immunology. Volume 117(2020:Jan.)
• Page Start: 73
• Page End: 83
• Publication Date: 2020-01
• Subjects: miR-223-3p microRNA-223-3p -- EAM experimental autoimmune myocarditis -- DCs dendritic cells -- tDCs tolerogenic dendritic cells -- Treg regulatory T cell -- IL-10 interleukin-10 -- TGF-β transforming growth factor-β -- NLRP3 NLR family protein containing a pyrin domain 3 -- PAMPs pathogen-associated molecular patterns -- DAMPs damage-associated molecular patterns -- ASC apoptosis-associated speck-like protein -- CARD caspase activation and recruitment domain -- mRNAs messenger RNAs -- IBD inflammatory bowel disease -- 3′-UTR 3′-untranslated region -- miRNAs microRNAs -- qRT-PCR quantitative reverse-transcription PCR -- BMDCs bone marrow-derived DCs -- LPS lipopolysaccharide -- PBS phosphate-buffered saline -- siRNA short interfering RNA -- imDCs immature DCs -- MLR mixed lymphocyte reaction -- RIPA radio immunoprecipitation assay -- SDS-PAGE sodium dodecyl sulphate-polyacrylamide gel electrophoresis -- PVDF polyvinylidene difluoride -- TBST Tris-buffered saline with Tween -- LVEDd left ventricular end-diastolic diameter -- LVEDs left ventricular end-systolic diameter -- IVSTd diastolic interventricular septum thickness -- PWTd posterior wall septum thickness -- H&E haematoxylin and eosin -- ROC receiver operating characteristic -- AUC area under the curve -- siNLRP3 NLRP3 siRNA -- siNC siRNA-negative control -- NC negative control; microRNA -- Tolerogenic dendritic cell -- Immune tolerance -- NLR family protein containing a pyrin domain 3 -- Experimental autoimmune myocarditis; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2019.10.027
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: miR-223-3p expression is downregulated in the serum of EAM mice. miR-223-3p overexpression favors a switch of LPS-stimulated DCs toward a tolerant phenotype. NLRP3 inflammasome is essential for the tolerogenic function mediated by miR-223-3p. miR-223-3p-overexpressing DCs ameliorate experimental autoimmune myocarditis in mice. Abstract: Autoimmune myocarditis is a cause of dilated cardiomyopathy and heart failure. MicroRNAs regulate many immune processes, but their role in aberrant inflammation during autoimmune myocarditis remains unclear. In this study, we investigated the role of miR-223-3p in experimental autoimmune myocarditis (EAM). We found that miR-223-3p expression was significantly lower in EAM mice than that in normal mice. miR-223-3p inhibited NLRP3 inflammasome expression, promoting the polarization of dendritic cells (DCs) towards a tolerogenic DC phenotype. miR-223-3p effectively induced regulatory T cell (Treg) generation by inhibiting the function of antigen-presenting DCs. Transfer of miR-223-3p-overexpressing DCs protected mice against the development of EAM. Our findings suggest that miR-223-3p is involved in the induction of the tolerogenic DC phenotype and regulates tolerance in autoimmune myocarditis.