MDA5 regulates bleomycin-induced proinflammatory response of macrophages

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.