Mannose Receptor Modulates Macrophage Polarization and Allergic Inflammation through miR-511-3p

Publication date: Available online 17 June 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Yufeng Zhou, Danh C. Do, Faoud T. Ishmael, Mario Leonardo Squadrito, Ho Man Tang, Ho Lam Tang, Man-Hsun Hsu, Lipeng Qiu, Changjun Li, Yongqing Zhang, Kevin G. Becker, Mei Wan, Shau-Ku Huang, Peisong Gao
BackgroundMannose receptor (MRC1/CD206) has been suggested to mediate allergic sensitization and asthma to multiple glyco-allergens, including cockroach allergens.ObjectiveDetermine the existence of a protective mechanism through which MRC1 limits allergic inflammation through its intronic miR-511-3p.MethodsWe examined the MRC1-mediated cockroach allergen uptake by lung macrophages and lung inflammation using C57BL/6 wild-type (WT) and Mrc1^-/- mice. 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-CMV-miR-511-3p-eGFP) was analyzed. Gene profiling of macrophages with or without miR-511-3p overexpression was also performed.ResultsMrc1^-/- lung macrophages showed 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 to WT mice. Macrophages from Mrc1^-/- mice showed significantly reduced levels of miR-511-3 and a M1 phenotype whereas over-expression 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 over-expression identified 729 differentially expressed genes, wherein the levels of Ptgds and its product PGD2 were significantly down-regulated by miR-511-3p. Ptgds showed a robust binding to miR-511-3p, which might contribute to the protective effect of miR-511-3p. The plasma levels of miR-511-3p were significantly lower in human asthmatics compared to non-asthmatic subjects.ConclusionThese studies support a critical but previously unrecognized role of MRC1 and miR-511-3p in protection against allergen-induced lung inflammation.

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