Clonal sharing of CD8+ T-cells links skin and joint inflammation in psoriatic arthritis

We hypothesised that skin and joint inflammation in psoriatic arthritis is linked in terms of CD8+ T-cell phenotype and clonality. We employed scRNAseq to directly compare the transcriptional signature and T-cell receptor repertoire of memory T-cells from paired skin and synovial tissue+/-fluid from patients with psoriatic arthritis. We identified an enrichment of type-17 CD8+ tissue-resident memory (TRM) cells in both skin and joint, with a stronger IL-17 signature in the skin than the joint. Importantly, we identified several T-cell clones that are shared between the skin and the joint. Shared clones tended to have the same phenotype at both sites, characterised by increased expression of genes associated with a cytotoxic, tissue-resident phenotype. This supports the hypothesis that skin and joint inflammation is linked in terms of T-cell clonality and raises the possibility that specific T-cells migrate between these compartments to propagate inflammation across both sites. Single cell RNA and TCR sequencing analysis of memory T cells from blood, skin, synovial fluid and synovial tissue from patients with psoriatic arthritis