Biology subjects

Eckman, B.

Publications and source records attributed to Eckman, B..

3 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↗

bioRxiv2023

Monocyte subpopulations exhibit distinct TNF-dependent aging signatures.

Monocytes are a key cell type contributing to age-associated inflammation or inflammaging. Since monocytes have the potential to enter circulation and differentiate into macrophages in tissues, they are capable of having a systemic effect on health. Here, we characterize the effect of aging on the transcriptional regulation of monocyte subpopulations in the bone marrow. We find that aging classical (Ly6c high) and non-classical (Ly6c low) monocytes exhibit distinct transcriptional profiles. These were associated with changes to the epigenomic landscape driven by the activity of specific TFs that often had opposing effects in monocyte subpopulations. Next, we determined that the aging signature was diminished in TNF-KO mice indicating that monocytes are altered in a TNF-dependent manner. Finally, we found that a subset of the aging signature was triggered by TNF over-expression. Together, our results implicate key factors driving age-associated changes to the transcriptional regulation of monocyte subpopulations. This study provides a better understanding of the impact of aging on monocytes and identifies targets for future investigation aiming to improve health in aging.

genomics↗

bioRxiv2020

Macrophages drive the inflammatory phase in experimental osteoarthritis

Macrophages fulfill critical functions in maintaining tissue homeostasis in steady-state, as well as in inflammation and immune response. Inflammation is not considered a major driver of osteoarthritis (OA), but macrophages have been implicated in its pathogenesis. Here, we use two mouse models of experiment OA - collagenase-induced osteoarthritis (CIOA) and destabilization of the medial meniscus (DMM) - to quantify the immune cell infiltration into the knee joint during the early stages of disease. We find that the peak of inflammation occurs at day 3 in CIOA and is characterized by a transitory increase in neutrophils and monocytes and a longer-lived expansion of synovial macrophages. Macrophage sub-populations are disproportionally expanded with CX3CR1+ cells accounting for a larger proportion of the macrophage compartment. Transcriptional profiling demonstrates that synovial macrophages up-regulate inflammatory genes coinciding with peak inflammation and down-regulate genes associated with homeostasis and tissue-residence. Female mice exhibit a similar expansion of macrophages post-CIOA indicating that the inflammatory phase is not sex-specific. Finally, we find day 7 post-DMM is also characterized by increases in neutrophil, monocyte, and macrophage sub-population numbers. These results support a role for macrophages in early stages of OA through driving the inflammatory phase. Further investigation may elucidate potential targets for the prevention or attenuation of OA-associated cartilage damage.

immunology↗