CXCR3 and Restricted T Cells in Psoriatic Arthritis Inflammation Save

Research from Oxford University suggests a potential pathogenic role for the chemokine CXCR3 and clonally restricted CD8+ T cells in the pathogenesis of psoriatic arthritis (PsA) based studies of PsA synovial fluid samples obtained by arthrocentesis from 11 patients with large-joint oligo PsA.

These findings, published in Nature Communications, utilized single-cell studies of leukocytes from PsA joints, wherein they showed a 3-fold expansion of memory CD8 T cells in the joints of PsA patients (compared to peripheral blood) and single-cell RNA sequencing of T cell receptor sequences showing marked CD8 T cell clonal expansions within PsA synovial fluids.

Transcriptome analyses of these synovial CD8 T cells showed evidence of clonal convergence, suggesting a single putative antigen may underly the development of inflammatory arthritis seen in nearly one-third of psoriasis patients. They also identified the chemokine receptor CXCR3 as being upregulated in the expanded synovial CD8 T cells, while two CXCR3 ligands (CXCL9 and CXCL10) also found in abundance in PsA synovial fluid.

Thus, in addition to the oligoclonality of T cells within PsA joints (suggesting the the same receptors are being engaged), they also found preferential presence of CXCR3 and its ligands that direct chemotaxis of leukocytes to the inflammed joint. 

These T cell findings suggest as a common trigger for PsA and a key role for the chemokine receptor CXCR3 in PsA pathogenesis; and both facets could be therapeutically exploited.