Monocytes in rheumatoid and psoriatic arthritis follow distinct inflammatory paths

Circulating monocytes in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are not uniform players in joint inflammation. A study published in Arthritis Research & Therapy reports that CD14-positive monocytes from patients with these two conditions respond to inflammatory stimulation in measurably different ways, spanning cytokine production, cellular metabolism, epigenetic marking and effects on bone-forming precursor cells. The findings position these blood-borne immune cells as contributors to the divergent pathology seen in inflammatory arthritis.

The research team isolated CD14-positive monocytes from the peripheral blood of RA patients, PsA patients and healthy controls, then stimulated the cells with lipopolysaccharide (LPS), a bacterial component that provokes a strong inflammatory response. They also generated monocyte-derived macrophages using M-CSF and polarised them towards M1 and M2 states. Gene expression was measured by RT-PCR, cell-surface markers by flow cytometry, and real-time metabolic activity by Seahorse extracellular flux analysis.

Upon LPS stimulation, monocytes from RA patients produced higher levels of IL-6, IL-1β, CXCL10, CXCL11, SLAMF1 and SLAMF2 than PsA monocytes, with both patient groups exceeding healthy controls. SLAMF3, by contrast, was significantly decreased. The heightened inflammatory output was paralleled by impaired endocytic capacity, a shift towards a glycolytic metabolic profile and evidence of dysfunctional mitochondria. Notably, RA monocytes showed more pronounced metabolic reprogramming than PsA monocytes, suggesting the two diseases rewire immune cell energetics to different degrees.

Activation and macrophage-associated markers, including CD40, CD64, CD206, CD163 and SLAMF7, were more frequently expressed and more highly expressed on classical and intermediate monocytes from both RA and PsA patients compared with healthy controls. When monocytes were differentiated into macrophages in the laboratory, the resulting cells retained the hyper-inflammatory behaviour and impaired endocytic capacity of their precursor monocytes, indicating that these features persist through differentiation rather than being erased.

The two diseases also diverged in how their monocytes influenced mesenchymal stem cells (MSCs), the bone marrow-resident precursors relevant to bone repair. When MSCs were cultured with conditioned media from patient monocytes, PsA monocyte-derived media preferentially enhanced the osteogenic function of MSCs, whereas RA monocyte-derived media predominantly induced MSC migration. This disease-biased difference in monocyte secretory activity may help explain why RA and PsA affect bone and tissue remodelling in distinct ways.

Epigenetic analysis added a further layer. The histone modifications H3K27ac and H3K4me3 were increased on classical and intermediate monocytes from both patient groups, consistent with baseline epigenetic priming of inflammatory gene programmes before any stimulation. In addition, the DNA-modifying enzymes TET2 and TET3 were further induced when the monocytes were exposed to LPS, implying that inflammatory signalling recruits both histone-level and DNA-level epigenetic machinery in these cells.

The study also tested whether a commonly used anti-inflammatory drug could influence these epigenetic responses. The glucocorticoid budesonide suppressed the LPS-induced TET2 and TET3 expression in RA and PsA monocytes, and this suppression was accompanied by inhibition of pro-inflammatory cytokine production. The authors present this as a parallel effect observed in the experimental system rather than a demonstration of clinical efficacy, since the work was conducted on isolated cells rather than in patients.

Finally, the researchers compared monocytes circulating in the blood with those recovered from the synovial compartment of the joint. Synovial monocytes displayed an activated, macrophage-like phenotype relative to their circulatory counterparts, consistent with the idea that monocytes entering the joint undergo further activation in the inflamed tissue environment.

The authors conclude that RA and PsA CD14-positive monocytes exhibit metabolic and functional reprogramming associated with distinct disease-biased effector profiles, alongside evidence of epigenetic priming at baseline and inducible responses following LPS stimulation. As an ex vivo study of patient-derived cells, it characterises cellular behaviour in the laboratory rather than establishing clinical outcomes, and the article was published as a peer-reviewed accepted manuscript that remains subject to final editorial edits. Nevertheless, the work highlights circulating monocytes as key contributors to the divergent pathology of inflammatory arthritis and offers candidate mechanisms, from glycolytic shifts to TET enzyme induction, that could be explored in future research.

Subject of Research: Distinct inflammatory, metabolic and osteogenic properties of monocytes in rheumatoid arthritis and psoriatic arthritis

Article Title: Rheumatoid arthritis and psoriatic arthritis monocytes display distinct pro-inflammatory, metabolic and osteogenic capacities

Article References: Amaechi, S., Gilmore, A., Hanlon, M. M., Tynan, O., O’Dowd N, N., Anton, D., Marginean, L., Darcy, H., Sundanum, S., Orr, C., Veale, D. J., Marzaioli, V., & Fearon, U. (2026). Rheumatoid arthritis and psoriatic arthritis monocytes display distinct pro-inflammatory, metabolic and osteogenic capacities. Arthritis Research & Therapy. https://doi.org/10.1186/s13075-026-03912-9

Image Credits: AI Generated

DOI: 10.1186/s13075-026-03912-9

Keywords: rheumatoid arthritis, psoriatic arthritis, monocytes, macrophages, inflammation, metabolism, epigenetics, glycolysis, mesenchymal stem cells, osteogenesis, TET2, budesonide