Gpnmb and Spp1 mark a conserved macrophage injury response masking fibrosis-specific programming in the lung

• DOI: 10.1172/jci.insight.182700
• Publication Date: 2024-11-07T17:56:56Z
• Authors: Emily M. King; Yifan Zhao; Camille M. Moore; Benjamin Steinhart; Kelsey C. Anderson; Brian Vestal; Peter K. Moore; Shannon A. McManus; Christopher M. Evans; Kara J. Mould; Elizabeth F. Redente; Alexandra L. McCu...; William J. Janssen

Macrophages are required for healthy repair of the lungs following injury, but they also implicated in driving dysregulated with fibrosis. How these two distinct outcomes lung injury mediated by different macrophage subsets is unknown. To assess this, single-cell RNA sequencing was performed on macrophages isolated from mice treated lipopolysaccharide or bleomycin. were categorized based anatomic location (airspace versus interstitium), developmental origin (embryonic recruited monocyte-derived), time after inflammatory challenge, and model. Analysis integrated dataset revealed that subset clustering driven tissue compartment rather than Gpnmb-expressing enriched genes typically associated fibrosis present both models. Analogous GPNMB-expressing identified datasets fibrotic non-fibrotic disease humans. We conclude this represents a conserved response to not sufficient drive Beyond response, we failed gain resident-like programming during repair. Overall, dictated dynamic shifts persistence macrophages.