M2 polarized macrophages can promote the activation of fibroblasts,735 releasing a large amount of factors such as TGF-β, PDGF, and CCL18, which further promote tissue fibrosis.736 In SSc, immune complexes in patients can induce monocytes to secrete secreted phosphoprotein 1 (SPP1),737 macrophage colony-stimulating factor (M-CSF), and IL-6.738 These factors collectively influence the disease process: SPP1 can promote the activation and migration of lung fibroblasts. This evidence concerns the gene SPP1 and systemic sclerosis.