A single-cell sequencing analysis has revealed clonal expansion of pro-inflammatory synovial CD8 T cells in psoriatic arthritis, providing further insight into the cellular immune landscape of this debilitating disease.
Psoriatic arthritis
Psoriatic arthritis (PsA) is a devastating immune-mediated inflammatory joint disease, commonly affecting patients with skin psoriasis. The pathogenesis of PsA is complex, involving several inflammatory pathways. Researchers believe PsA is largely driven by immune cells entering or proliferating within the joint synovial lining tissue and/or fluid. Genome-wide association studies have indicated a potentially pathogenic role for CD8 T cells in PsA. Studies have also reported presence of these cells within the synovial fluid of some patients.
Single-cell resolution
In a study, published in Nature Communications, researchers from the University of Oxford and the Wellcome Sanger Institute used complementary single-cell approaches to study the cellular landscape of PsA blood, synovial fluid and tissue. They used 5’ chromium technology to unravel the architecture of T cells in the synovial fluid compared to peripheral blood.
Through mass cytometry and T-cell receptor VDJ sequencing, the team found striking expansions of memory CD8 and CD4 T cells in the synovial fluid of patients with PsA. Specifically, they found a 3-fold increase of memory CD8 T cells in the joints compared to blood of PsA patients. Transcription analyses revealed that CD8 T cells in the synovial fluid, synovial tissue and peripheral blood expressed cycling, activation, tissue-homing and tissue residency markers. Interestingly, they identified T-cell receptor convergence in patient synovial clones. Together, these results provide further evidence to support PsA as a MHC-I peptide antigen complex driven disease. The team also observed upregulation of the chemokine receptor, CXCR3, within expanded synovial CD8 T cells. Additionally, they found elevated levels of CXCR3 ligands, CXCL9 and CXCL10, in PsA synovial fluid.
Step forward
Dr Hussein Al-Mosswi, University of Oxford, stated:
“Our data suggest that psoriatic arthritis doesn’t just appear out of nowhere. Each receptor is like a unique lock that recognises a molecular key and we discovered, that across the patients, they are recognising a common molecule. This gives the first evidence that the T cells are seeing and reacting to the same molecule, which acts as a trigger for the disease. We don’t know the exact culprit yet, but this a great step forward in understanding the disease.”
These results provide further insight into the pathogenesis of PsA and other HLA-associated immune-mediated inflammatory diseases. It raises the possibility that CXCR3+ CD8 T cells play a key role in executing localised inflammation in PsA. Therefore, the team believe that these cells could represent an attractive therapeutic target for patients with PsA.
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