Peisong Gao
Johns Hopkins University School of Medicine, USA
Title: Mannose receptor regulates macrophage polarization and allergic inflammation through MiR-511-3p
Biography
Biography: Peisong Gao
Abstract
We proposed the existence of a protective mechanism through which mannose receptor (MRC1/CD206) limits allergic inflammation via allergen clearance and its intronic miRNA511-3p. Mrc1-null (Mrc1-/-) mice showed significant reduction in cockroach allergen uptake compared with WT mice and consequently Mrc1-/- mice had greater lung inflammation, IgE levels and cytokine production in a cockroach allergen-induced mouse model compared to WT mice. MiR-511-3p, encoded within the MRC1 gene was shown to be co-regulated with Mrc1. Macrophages from Mrc1-/- mice showed significantly reduced levels of miR-511-3p and a M1 phenotype whereas over-expression of miR-511-3p rendered macrophages to exhibit a M2 phenotype. Further, delivery of miR-511-3p in mice led to a significant reduction in cockroach allergen-induced inflammation and this effect was confirmed in the bone-marrow chimeric mice receiving hematopoietic stem and progenitor cells (HS/PCs) over expressing miR-511-3p. The serum levels of miR-511-3p were significantly lower in human asthmatics compared to non-asthmatic subjects. Profiling of macrophages with or without miR-511-3p over-expression identified 729 differentially expressed genes, wherein the level of ptgds2, encoding PGD2 synthase and its product, PGD2 was significantly lower, which might contribute to the protective effect of Mrc1 and miR-511-3p. Collectively, these studies suggest that Mrc1 and its intronic miR-511-3p mediate protection against allergen-induced lung inflammation.
