CX3CR1 And MHCII Define Distinct Synovial Macrophage Populations With Conserved Inflammatory Response Across Mouse Models Of Rheumatoid Arthritis.

Wang, Y.; Chen, S.-Y.; Homan, P.; Montgomery, A.; Maciuch, J.; Dowling, S. D.; Dominguez, S.; Gadhvi, G.; Therron, T. A.; Eckman, B.; Teodosio, A.; Howdle, D.; Manada De Lobos, V.; Khan, M. D.; Mian, K.; Dapas, M.; Filer, A.; Cuda, C. M.; Perlman, H.; Winter, D. R.

doi:10.64898/2026.07.30.741914

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bioRxiv · 10.64898/2026.07.30.741914

CX3CR1 And MHCII Define Distinct Synovial Macrophage Populations With Conserved Inflammatory Response Across Mouse Models Of Rheumatoid Arthritis.

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Abstract

Macrophages in the synovial lining are critical for the maintenance of healthy tissue while also contributing to the pathogenesis of rheumatoid arthritis (RA). However, the field currently lacks a unifying characterization of synovial macrophage heterogeneity across steady-state and inflammation. Here, we defined 4 transcriptionally distinct populations of synovial macrophages CX3CR1+MHCII- (lining); CX3CR1-MHCII- (interstitial/sublining); CX3CR1-MHCII+ (monocyte-derived); and CX3CR1+MHCII+ (infiltrating). The MHCII-populations are long-lived and derived from embryonic precursors regardless of localization while the MHCII+ populations differentiate from bone marrow (BM) progenitors dependent on CCR2. We identified conserved activation pathways between acute and chronic mouse models of inflammatory arthritis as well as novel arthritis-associated subpopulations. During peak inflammation, the influx of BM-derived cells was associated with upregulation of monocyte-related genes with concurrent down-regulation of tissue-resident genes. Our results provide a unifying schema for describing synovial macrophages across conditions and pave the way for future studies in modulating transcriptional activity in rheumatoid arthritis.

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Wang, Y., Chen, S.-Y., Homan, P., Montgomery, A., Maciuch, J., Dowling, S. D., Dominguez, S., Gadhvi, G., Therron, T. A., Eckman, B., Teodosio, A., Howdle, D., Manada De Lobos, V., Khan, M. D., Mian, K., Dapas, M., Filer, A., Cuda, C. M., Perlman, H., Winter, D. R.. 2026-08-04. CX3CR1 And MHCII Define Distinct Synovial Macrophage Populations With Conserved Inflammatory Response Across Mouse Models Of Rheumatoid Arthritis.. https://doi.org/10.64898/2026.07.30.741914

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