Mannose receptor modulates macrophage polarization and allergic inflammation through miR-511-3p - 05/01/18
, Peisong Gao, MD, PhD a, ⁎ Abstract |
Background |
Mannose receptor (MRC1/CD206) has been suggested to mediate allergic sensitization and asthma to multiple glycoallergens, including cockroach allergens.
Objective |
We sought to determine the existence of a protective mechanism through which MRC1 limits allergic inflammation through its intronic miR-511-3p.
Methods |
We examined MRC1-mediated cockroach allergen uptake by lung macrophages and lung inflammation using C57BL/6 wild-type (WT) and Mrc1−/− mice. The role of miR-511-3p in macrophage polarization and cockroach allergen–induced lung inflammation in mice transfected with adeno-associated virus (AAV)–miR-511-3p (AAV–cytomegalovirus–miR-511-3p–enhanced green fluorescent protein) was analyzed. Gene profiling of macrophages with or without miR-511-3p overexpression was also performed.
Results |
Mrc1−/− lung macrophages showed a significant reduction in cockroach allergen uptake compared with WT mice, and Mrc1−/− mice had an exacerbated lung inflammation with increased levels of cockroach allergen–specific IgE and TH2/TH17 cytokines in a cockroach allergen–induced mouse model compared with WT mice. Macrophages from Mrc1−/− mice showed significantly reduced levels of miR-511-3 and an M1 phenotype, whereas overexpression of miR-511-3p rendered macrophages to exhibit a M2 phenotype. Furthermore, mice transfected with AAV–miR-511-3p showed a significant reduction in cockroach allergen–induced inflammation. Profiling of macrophages with or without miR-511-3p overexpression identified 729 differentially expressed genes, wherein expression of prostaglandin D2 synthase (Ptgds) and its product PGD2 were significantly downregulated by miR-511-3p. Ptgds showed a robust binding to miR-511-3p, which might contribute to the protective effect of miR-511-3p. Plasma levels of miR-511-3p were significantly lower in human asthmatic patients compared with nonasthmatic subjects.
Conclusion |
These studies support a critical but previously unrecognized role of MRC1 and miR-511-3p in protection against allergen-induced lung inflammation.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Mannose receptor, miR-511-3p, macrophage, asthma
Abbreviations used : AAV, AF, BAL, BM, CLR, CMV, CRE, DC, FDR, FITC, GFP, H&E, LTBP1, LV, M-CSF, miRNA, MRC1, PAS, PTGDS, qPCR, ROCK2, SSC, TLR4, WT
Plan
| Supported by grants from the US National Institutes of Health (NIH; RO1ES021739, R21 AI109062, and R21 AI121768) and the National Science Foundation of China (NSFC; 81628001; to P.G.); the Intramural Research Program of the National Institutes of Health, National Institute on Aging; the China 1000 Young Talents Plan Program (to Y.Z.); and Fudan Children's Hospital and Fudan University for Initial Funding, NSFC 81671561, and MOST 2016YFC1305102 (to Y.Z.); and by grants from the National Health Research Institutes (EOPP10-014 and EOSP07-014 to S.-K.H.) and the Ministry of Health (EODOH01; to S.-K.H.); Academia Sinica (AS-105-TP-B05 to SK Huang); and Kaohsiung Medical University “Aim for the Top Universities Grant” and “the Talent Plan” (KMU-TP-105A04 and KMU-SH000184 to SK Huang), Taiwan. |
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| Disclosure of potential conflict of interest: Y. Zhou has received grants from the China 1000 Young Talents Plan Program, Fudan Children's Hospital and Fudan University for Initial Funding, NSFC 81671561, and MOST 2016YFC1305102. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 141 - N° 1
P. 350 - janvier 2018 Retour au numéro
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