Arthritis-required tissue-resident monocyte-lineage cells (TR-MC) exist as three subsets in mouse synovial tissue 3335

Abstract Description Monocytes are critical for rheumatoid arthritis (RA), but their depletion does not rescue the disease in mouse models. We identified tissue-resident monocyte lineage cells (TR-MC) as essential for acute RA-like disease in mice, though their ontogeny and functions remain unclear. Here, we identified bone marrow (BM)-derived and long-lived TR-MC in CD45.1 → CD45.2 B6 bone marrow chimera (BMC) and parabiosis mice. CITE-seq of BMC validated the heterogeneity and further classified TR-MC into one BM-derived and two long-lived TR-MC subsets, marked by Ccr2, Cd163, and Cx3cr1, with gene ontology showing long-lived TR-MC are enriched in homeostasis processes, while BM-derived TR-MC are linked to adaptive immunity. Comparing the numbers of TR-MC subsets within reciprocal Ccr2-/- & CD45.1 BMC and parabiosis pairs, BM-derived TR-MC were significantly reduced in Ccr2-/- → CD45.1 BMC and Ccr2-/- pair, indicating their Ccr2 dependence. On day 7 post clodronate liposome treatment, BM-derived TR-MC upregulated Plac8 and Il1b expression, indicating they were newly replenished from circulation and responsive to synovial niche disruption. During the development of RA-like arthritis in mice, CITE-seq revealed novel BM-derived TR-MC at the peak and plateau stages. At these stages, BM-derived TR-MC outnumbered long-lived TR-MC, with subset ratios returning to steady-state levels during recovery. These findings highlight the heterogeneity of TR-MC and their central role in arthritis development. Funding Sources Supported by NIAMS: 5R01AR080513-03 Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)