Cellular origins and functions of synovial macrophages in homeostatic and inflammatory arthritis
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Macrophages are an important cell type well known for its’ role in the immune system. Macrophages have two hematopoietic sources; they can be derived from hematopoietic stem cell (HSC) progenitors or erythro-myeloid progenitors (EMP). Synovial macrophages exist within the normal healthy joint, but the current origins and functions of these cells are unclear, including those involved in inflammatory arthritis (IA). To explore the origins of the synovial macrophages we utilized both cell lineage-tracing models and an arthritic model, K/BxN mice serum transfer arthritis (STA). We used Flt3Cre;Rosa26LSL-YFP mice to label HSC-derived cells and Cx3cr1CreERT2;Rosa26LSL-tdTomato and CSF1rmericremer;Rosa26LSL-tdTomato mice to label EMP-derived cells. Our histological data showed a unique population of EMP derived synovial tissue resident macrophages that was present in mice at ages E16.5 and P0 (neonate). Additionally, we found that HSC-derived cells do not significantly contribute to synovial macrophage populations throughout development. Interestingly, in arthritic conditions, we detected a dramatic increase in HSC-derived synovial macrophages in the inflamed synovium. Using macrophage markers F4/80 and CD68 we were able to fluorescently label and identify three different subtypes of synovial macrophages that exist within the joint in both homeostatic and arthritic conditions. Although further studies need to be completed, we have taken a pivotal step towards characterizing synovial macrophages in healthy and arthritic mice.