miR-511-3p protects against cockroach allergen-induced airway inflammation

Plasma miR-511-3p levels are lower in asthmatics compared to healthy controls. MiR-511-3p, encoded within the mannose receptor (Mrc1) gene, is transcriptionally co-regulated with Mrc1. MiR-511-3p delivery reversed the increased airway inflammation in cockroach allergen (CRE)-induced mouse model of asthma due to Mrc1-deficiency. We provided additional evidence to support the protective role of miR-511-3p in allergen-induced airway inflammation. miR-511-3p-deficient (miR-511-3p-/-) mice were generate using the CRISPR-Cas9 system and back-crossed with WT mice for a minimum of five generations. miR-511-3p-/- genotype was confirmed by sequencing. MiR-511-3p-/- and WT mice were subjected to our well-established CRE-induced asthma model. Backcrossed miR-511-3p-/- mice were confirmed by genotyping and Sanger sequencing. MiR-511-3p levels are increased in WT, but were undetectable in miR-511-3p-/- mice after CRE-challenge. Similar expression of Mrc1 was observed in both animals. Interestingly, MiR-511-3p-/- mice have higher airway inflammation after CRE-challenged compared to WT controls. Histological examination showed increased dense peribronchial infiltrates, goblet hyperplasia, higher recruitment of inflammatory cells to the lungs, especially with eosinophils, elevated levels of serum titers of cockroach-specific IgE/IgG1, levels of IL-4 and IL-13, but lower levels of IFN-gamma, in the BALFs of miR-511-3p-/- compared to WT controls. Our initial findings firmly support a protective role of miR-511-3p in allergen-induced allergic inflammation making it an attractive therapeutic agent for the treatment of asthma and allergic diseases.