microRNA regulates alveolar macrophage maintanance and function during pulmonary fibrosis

Alveolar macrophages (AMs) are important for maintaining lung homeostasis and involved in many lung diseases such as pulmonary fibrosis. Tissue-resident AMs (TR-AMs) derived from embryonic progenitors can self-renew locally in the steady state independently of hematopoiesis. During fibrogenesis, circulating monocytes rapidly migrate into the lung and become monocyte-derived AMs (Mo-AMs). MicroRNAs (miRNAs) are non-coding small RNAs that are essential for regulating gene expression and processed by ribonuclease Dicer. However, the role of miRNAs in regulation of TR-AMs and Mo-AMs during pulmonary fibrosis remains poorly understood. Bulk RNA-seq analysis revealed divergent transcriptomic and pathway changes caused by miRNA deficiency in the two AM subgroups after BLM injury. We propose that miRNAs are key epigenetic mediators that differentially regulate TR-AM and Mo-AM maintenance and function in the pathogenesis of pulmonary fibrosis. Overall design: RNA-sequencing of TR-AMs and Mo-AMs sorted from Cd11cCre+Dicerfl/fl and Cd11cCre-Dicerfl/fl adult mice on day 14 after bleomycin treatment