MDA5 regulates bleomycin-induced proinflammatory response of macrophages

The role of innate immune receptors recognizing RNA and self RNA in lung inflammation and fibrosis formation is not well understood. Here, we demonstrate melanoma differentiation-associated gene 5 (MDA5) regulates bleomycin-induced lung fibrosis, accompanied by increased IL-17+ γδ T cells and neutrophils compared to wild-type (WT) mice. Lung CD11b+ macrophages, with similar characteristics of human Spp1+ macrophages, displayed unique gene expression profiles, marked by elevated levels of ligands for CCR2 and collagen production. Moreover, MDA5 was found to regulate these ligands in bleomycin-treated bone marrow-derived macrophages and U937 cells, contributing to the clearance of extracellular RNA. In conclusion, our findings suggest that MDA5 plays a pivotal role in regulating bleomycin-induced lung fibrosis through influencing the interplay among macrophages, lymphocytes, and neutrophils.