Our data supported two conclusions: first, massively aggregated TREM2-dependent macrophages play a protective role during skin fibrosis in a mouse model and human SSc; second, diseases-associated TREM2+ MФs in pathological skin fibrosis have a fetal-like reprogramming similar to fetal skin counterparts to maintain skin homeostasis, but each has merits in skin remodeling and development (Figure 7). The gene discussed is TREM2; the disease is systemic sclerosis.