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

Abstract

Objective: Psoriatic arthritis (PsA) is an HLA class I-associated inflammatory arthritis that develops in up to 30% of people with psoriasis. We tested the hypothesis that skin and joint inflammation in PsA is linked in terms of CD8+ T-cell phenotype and clonality.

Methods: Using scRNAseq (n=6 skin with n=5 paired synovial tissue and/or n=5 paired synovial fluid) and spatial transcriptomics (n=1 paired skin and synovial biopsies, n=4 unpaired biopsies), we compared the transcriptional signature, T-cell receptor repertoire and cell neighbourhoods of T-cells from skin and synovial tissue and/or fluid from patients with PsA.

Results: We identified an enrichment of type-17 CD8+ tissue-resident memory (T_RM) T-cells in both skin and joint, with a stronger IL-17 signature in the skin than the joint. CD8+ T_RM cells resided in distinct cell neighbourhoods in skin and joint but were located adjacent to antigen-presenting cells in both sites. Several T-cell clones were shared between the skin and joint. Across the six patients, 155 CD8+ T-cell clones were shared between the two sites, comprising 1,071 CD8+ T cells and taking up a median of 13% of the skin and 8% of the joint CD8+ TCR repertoire. CD8+ skin-joint shared clones tended to have a similar phenotype at both sites, characterised by increased expression of genes associated with a cytotoxic, tissue-resident phenotype.

Conclusion: Our findings support the hypothesis that skin and joint inflammation in PsA is linked in terms of CD8+ T-cell clonality and that specific T-cells migrate between these compartments to propagate inflammation across both sites.