Therapeutic strategies targeting pro-fibrotic macrophages in interstitial lung disease

Idiopathic pulmonary fibrosis (IPF) is the representative phenotype of interstitial lung disease where severe scarring develops in the lung interstitium. Although antifibrotic treatments are available and have been shown to slow the progression of IPF, improved therapeutic options are still needed. Recent data indicate that macrophages play essential pro-fibrotic roles in the pathogenesis of pulmonary fibrosis. Historically, macrophages have been classified into two functional subtypes, M1 & DPRIME;and M2, and it is well described that M2 & DPRIME;or alternatively activated macrophages contribute to fibrosis via the production of fibrotic mediators, such as TGF-8, CTGF, and CCL18. However, highly plastic macrophages may possess distinct functions and phenotypes in the fibrotic lung environment. Thus, M2-like macrophages in vitro and pro-fibrotic macrophages in vivo are not completely identical cell populations. Recent developments in transcriptome analysis, including single-cell RNA sequencing, have attempted to depict more detailed phenotypic characteristics of pro-fibrotic macrophages. This review will outline the role and characterization of pro-fibrotic macrophages in fibrotic lung diseases and discuss the possibility of treating lung fibrosis by preventing or reprogramming the polarity of macrophages. We also utilized a systematic approach to review the literature and identify novel and promising therapeutic agents that follow this treatment strategy.

Automated summary

Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease characterized by severe scarring in the lung interstitium. Macrophages play a crucial role in the development of pulmonary fibrosis, and recent studies have revealed the heterogeneity and plasticity of pro-fibrotic macrophages. This review discusses the role and characterization of pro-fibrotic macrophages in fibrotic lung diseases and explores the potential of targeting macrophage polarity as a therapeutic strategy for lung fibrosis.