To determine the origin of these macrophages, we examined tissue residency genes including LYVE1, TIMD4, TREM2, FOLR2, C1QA, VSIG4, and TGFBR2A. A significant increase in all “tissue-resident”–associated genes in synovial tissue CD206+CD163+ macrophages compared to double-negative CD206−CD163− macrophages, RA synovial fluid CD206+CD163+ macrophages, and RA M1 macrophages was observed (Fig. 3D, P < 0.01; P < 0.05; P < 0.001 respectively). The gene discussed is TREM2; the disease is rheumatoid arthritis.