Biology subjects

Mian, K.

Publications and source records attributed to Mian, K..

2 recordsLinked to original sources

bioRxiv2026

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

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.

immunology↗

bioRxiv2025

Cellular composition of tissue-resident monocyte-lineage cells reveal functional heterogeneity during inflammatory arthritis

Tissue-resident monocyte-lineage cell (TRMC) are an extravascular population distinct from circulating monocytes and synovial macrophages and are critical for the development of inflammatory arthritis. However, the precise identities and origins of TRMC subpopulations remain unclear. Here, we characterize the ontogeny of TRMC, which are comprised of bone-marrow (BM)-derived and an embryonic, long-lived population. Furthermore, we identified three TRMC subpopulations, distinguished by expression of TIM4, CX3CR1, and MHCII. Clodronate-laden liposome reduces the number of TRMC but does not impact the proportions or transcriptional profile of TRMC subpopulations at 7 days post administration. TIM4+CX3CR1+ and TIM4+ TRMC represent long-lived population, whereas MHCII+ TRMC are BM-derived and dependent on Ccr2 during steady state. BM-derived TRMC expand and replenish the TIM4+CX3CR1+ and TIM4+ TRMC compartments throughout the peak and plateau of inflammatory arthritis. These findings underscore the importance heterogeneity within TRMC and highlight their distinct responses to synovial disruption and potential roles in rheumatoid arthritis (RA).

immunology↗