The emerging roles of interstitial macrophages in pulmonary fibrosis: A perspective from scRNA-seq analyses

Abstract

Pulmonary fibrosis is an irreversible and progressive disease affecting the lungs, and the etiology remains poorly understood. This disease can be lethal and currently has no specific clinical therapeutic regimen. Macrophages, the most common type of immune cell in the lungs, have been reported to play a key role in the pathogenesis of fibrotic disease. The lung macrophage population is mostly composed of alveolar macrophages and interstitial macrophages, both of which have not been thoroughly studied in the pathogenesis of lung fibrosis. Interstitial macrophages have recently been recognised for their participation in lung fibrosis due to new technology arising from a combination of bioinformatics and single-cell RNA sequencing analysis. This paper reviews recent developments regarding lung macrophage classification and summarizes the origin and replenishment of interstitial macrophages and their function in pulmonary fibrosis.

Innate Immune Training Initiates Efferocytosis to Protect against Lung Injury

“…[ 41 ] Meanwhile, a recent study showed that β‐glucan elicits lung interstitial macrophage training and that lung interstitial macrophages play a crucial role in PF. [ 40 , 45 ] In our single cell RNAseq analysis of whole lungs of untrained and β‐glucan‐trained mice, the relative number of interstitial macrophages (F4/80, CD11b, CX3CR1; CX3CR1, CCR2, MafB, MHCII [H2‐Eb1, H2‐Aa, and H2‐Ab1]) in the lungs of trained mice underwent dynamic alterations during the course of lung injury (data not shown). On day 4 after the sham/bleomycin instillation, there was an increase in lung interstitial macrophages of trained mouse in the absence of injury.…”

Endothelial Erg Regulates Expression of Pulmonary Lymphatic Junctional and Inflammation Genes in Mouse Lungs Impacting Lymphatic Transport

“…Whole lung microarray and gene clustering analysis highlighted a collective upregulation of pro-inflammatory and fibrosis genes in the Erg-CKO lungs. High infiltration of LY6C+ monocytes 30 , cDC1 antigen presentation cells 54 , and anti-inflammatory interstitial macrophages 32 collectively suggested an increased inflammatory predisposition in Erg-CKO lungs. Upregulation of key fibrotic genes (Ccn2, Pai1) and inflammatory genes (Tgfβ, Ifnγr1 and Ifnγr2) in Erg-CKO lung further indicated a possible predisposition to fibrosis [55][56][57][58][59] .…”

Integrative single‐cell transcriptome analysis provides new insights into post‐COVID‐19 pulmonary fibrosis and potential therapeutic targets

“…41 These results in spatial levels, support that fibroblast and infiltrated macrophages were key pathology players in PCPFs. and pirfenidone effectively reversed the expression of lung fibrosisrelated genes, including syndecan-2 (SDC2), 42 PLA2G7, 43 and serpin family G member 1 (SERPING1), 44 common to COVID-19, IPF, and TGF-β1-induced lung fibrosis transcriptomes.…”

“…We analyzed the impact of antifibrotic drugs on the transcriptome of a rat model of TGF‐β1‐induced lung fibrosis. Nintedanib, sorafenib, and pirfenidone effectively reversed the expression of lung fibrosis‐related genes, including syndecan‐2 ( SDC2 ), 42 PLA2G7 , 43 and serpin family G member 1 ( SERPING1 ), 44 common to COVID‐19, IPF, and TGF‐β1‐induced lung fibrosis transcriptomes.…”