Clonal sharing of CD8+ T-cells links skin and joint inflammation in psoriatic arthritis
Lucy E. DurhamiD, Frances HumbyiD, Nora Ng, Roman LaddachiD, Elizabeth H. Gray, Sarah E. RyaniD, Kathryn J. A. SteeliD, Rosie RossiD, Giovanni A. M. PovoleriiD, Rosamond A. NuamahiD, Kathy FungiD, Athul Menon Kallayil, Pawan DhamiiD, Bruce W KirkhamiD, Leonie S. TaamsiD
Abstract
We hypothesised that skin and joint inflammation in psoriatic arthritis (PsA) 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 and/or fluid from patients with PsA. We identified an enrichment of type-17 CD8+ tissue-resident memory (TRM) T-cells in both skin and joint, with a stronger IL-17 signature in the skin than the joint. Several T-cell clones were shared between the skin and joint and these shared clones tended to have the same signature at both sites, characterised by increased expression of genes associated with a cytotoxic, tissue-resident phenotype. Our findings support the hypothesis that skin and joint inflammation in PsA 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.
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