Study highlights potential for targeting macrophages to improve rheumatoid arthritis outcomes
· News-MedicalThis work was led by Professor Ursula Fearon and Dr Megan Hanlon from the Molecular Rheumatology Group in Trinity, and by Professor Douglas Veale, from St Vincent's University Hospital.
Combined, these findings identify the presence of an early pathogenic macrophage cell/gene signature that shapes the RA joint inflammatory environment and represents a unique opportunity for early diagnosis and therapeutic intervention.
KEY FINDINGS
Researchers:
- Identified a novel macrophage subtype in the joint and showed that these are the dominant macrophages in patients with active RA.
- Found this macrophage subtype is highly pro-inflammatory and releases proteins called cytokines that cause further inflammation in the joint.
- Identified that these cells also have the ability to activate other cell types (the fibroblast) in the joint that specifically invade and breakdown adjacent cartilage and bone.
- Identified that the frequency of this cell type in the joint at baseline predicted patients' response to treatment and subsequent disease flare.
- In parallel, the protective barrier macrophages (CX3CR1+) were depleted in established RA, showing a switch in the dominance of joint macrophages from protective macrophages to pro-inflammatory macrophages.
- Importantly, the identification of a dominant macrophage subtype (CD40-expressing CD206+CD163+) suggests targeting of CD40 signalling could represent a new strategy for patients who currently don't respond to treatment.
- Finally, and really importantly the team identified that these cells are present and become activated in individuals at risk of developing RA, thus prior to clinical signs and symptoms. Identification of the early cellular/gene patterns and cues that transform protective macrophage population into a dysfunctional pro-inflammatory macrophage may provide opportunities to target early and reinstate joint homeostasis in RA patients.
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