Extended Data Fig. 9: CLEC10a^pos, S100A12^pos and SPP1^pos STMs are located predominantly in the synovial interstitium.

a–c, Representative confocal microscopy images (40×) showing IF staining for CLEC10a (green) and macrophage marker CD68 (red) in (a) healthy synovium (b) active RA synovium, and (c) remission RA synovium. These show CLEC10a^posCD68^pos (solid white arrows) and CLEC10a^negCD68^pos (hollow white arrows) macrophages, and CLEC10a^posCD68^neg cells that are not macrophages. Inset images show CLEC10a^posCD68^pos macrophages at higher magnification. d-f, Synovial S10012A^pos STMs are scarce in healthy and remission RA but abundant in the sublining layer in active RA. Representative confocal microscopy images (40×) showing IHC staining for S10012A (green) and macrophage marker CD68 (red) in (d) healthy synovium (e) active RA synovium, and (f) remission RA synovium. These show S10012A^posCD68^pos (solid white arrows) macrophages only in active RA. S100A12A^negCD68^pos (hollow white arrows) macrophages and S100A12A^posCD68^neg cells are located throughout the synovial tissue. Inset images show S10012A^posCD68^pos macrophages at higher magnification. g-i, Synovial SPP1^pos STMs are scarce in healthy and remission RA but abundant in the sublining layer in active RA. Representative confocal microscopy images (40×) showing IF staining for SPP1 (green) and macrophage marker CD68 (red) in (g) healthy synovium, (h) active RA synovium (two patients), and (i) remission RA. These show SPP1^posCD68^pos (solid white arrows) macrophages and SPP1^negCD68^pos (hollow white arrows) macrophages. Inset images show SPP1^posCD68^pos macrophages at higher magnification. The nuclei are stained with DAPI (blue). Images representative of synovial tissue of healthy donors (n = 5), active RA (n = 6) and remission RA (n = 6) obtained in 3 independent experiments with similar results are shown. A, adipocyte; BV, blood vessel. Scale bars = 50 μm.