Spondyloarthritis & psoriatic arthritis
A CCL20+ macrophage subpopulation is the major producer of tumour necrosis factor (TNF) in axial spondyloarthritis synovium and is driven by CD40L and a myeloid autocrine circuit
Authors' conclusion
CCL20+ macrophages are a major CD40L- and IL-1β/TNF-α-driven source of TNF in AxSpA synovium. AxSpA circulating monocytes exhibit heightened basal CCL20+ signatures and inflammatory responsiveness that converge towards HC responses after inflammatory priming, supporting circulating CCL20+ monocytes as a marker of IL-1β/TNF-α-driven myeloid inflammation.
Study context
- Population
- Patients with axial spondyloarthritis (AxSpA) and healthy controls (HCs)patients with AxSpA whose synovial tissue underwent scRNA-seq
- Participants
- 5 patients
- Comparison
- AxSpA monocytes vs HC monocytes
- Outcome
- Source of TNF in AxSpA synovium
Methodological detailscomparisons with rheumatoid arthritis datasets, coculture of monocyte-derived macrophages with activated autologous CD4+ T cells, blocking and cytokine experiments
- Comparisons with rheumatoid arthritis datasets
- Coculture of monocyte-derived macrophages with activated autologous CD4+ T cells
- Blocking and cytokine experiments
Main finding
As reported in the abstract
- CCL20+ macrophages were the predominant source of TNF in AxSpA synovium, with TNF protein confirmed in tissue and synovial fluid
Further findings
Induction of the CCL20+ phenotype
- Activated CD4+ T cells induced the CCL20+ phenotype through CD40L-CD40 signalling and an IL-1β/TNF-α autocrine circuit in HC-derived and AxSpA-derived cells
Baseline CCL20+ signature of monocytes
- Baseline AxSpA monocytes showed a higher CCL20+ signature than HC monocytes, but this difference largely disappeared after T-cell-mediated induction
Cytokine production under stimulation
- AxSpA monocytes produced more TNF, IL-6, IL-1β, and IL-23 than HC monocytes, a difference attenuated following IL-1/TNF priming
Original publication
A CCL20+ macrophage subpopulation is the major producer of TNF in axial spondyloarthritis synovium and is driven by CD40L and a myeloid autocrine circuit. Ann Rheum Dis. Published 26 October 2026. doi:10.
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