Linking Skin and Joint Inflammation in Psoriatic Arthritis through Shared CD8⁺ T Cell Clones.

Abstract

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. Using single-cell RNA sequencing (n = 6 skin samples with n = 5 paired synovial tissue samples and/or n = 5 paired synovial fluid samples) and spatial transcriptomics (n = 1 paired skin and synovial biopsy sample, n = 4 unpaired biopsy samples), we compared the transcriptional signature, T cell receptor repertoire, and cell neighborhoods of T cells from skin and synovial tissue and/or fluid samples from patients with PsA. We identified an enrichment of type 17 CD8⁺ tissue-resident memory T (Trm) cells in both the skin and joint, with a stronger interleukin-17 signature in the skin than the joint. CD8⁺ Trm cells resided in distinct cell neighborhoods in the 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⁺ T cell receptor repertoire. CD8⁺ skin-joint shared clones tended to have a similar phenotype at both sites, characterized 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 CD8⁺ T cell clonality and that specific T cells migrate between these compartments to propagate inflammation across both sites.