Weishaupt, Chambers, et al. combine single-cell transcriptomic and epigenomic profiling with in vivo models to map the temporal dynamics of macrophage-fibroblast communication during inflammatory arthritis. They show that fibroblasts initiate inflammation, whereas monocyte-derived macrophages undergo transcriptional reprogramming into SPP1+ cells that actively promote resolution by restraining fibroblast pathogenicity.