Tissue-resident memory CD8+ T cells from skin differentiate psoriatic arthritis from psoriasis.

Objectives Studies that compare immune cell phenotype and function in psoriatic arthritis (PsA) versus psoriasis limited to cutaneous involvement (Pso) are scarce, yet critical to understand the pathogenesis of PsA. Methods First, in-depth immunophenotyping of different T cell and Dendritic cell subsets was performed in PsA, Pso, axial spondyloarthritis patients and healthy controls. Subsequently, we analyzed cells from peripheral blood, synovial fluid, and skin biopsies using flow cytometry, alongside high-throughput transcriptome analyses and functional assays on the specific cell population differentiating PsA from Pso. Results As compared to HC, the peripheral blood of PsA was characterized by an increase of regulatory CD4 T cells and IL-17A & IL-22 co-producing CD8+ T cells. One population specifically differentiated PsA from Pso: CCR10+ CD8+ T cells, being enriched in PsA. CCR10+ CD8+ T cells were phenotypically DNAM1hi , effector memory cells that co-expressed skin homing receptors CCR4 and CLA. CCR10+ CD8+ T cells were detected under inflammatory and homeostatic conditions in skin, but were not enriched in synovial fluid. Gene profiling further revealed that CCR10+ CD8+ T cells expressed GATA3, FOXP3, and core transcriptional signature of tissue-resident memory T cells, including CD103. Specific genes (including RORC, IFNAR1, ERAP1) were upregulated in PsA compared to Pso. CCR10+ CD8+ were endowed with Tc2/22-like cytokine profile, lacked cytotoxic potential, and displayed overall regulatory function. Conclusion Tissue-resident memory CD8+ T cells derived from the skin are enhanced in the circulation of PsA as compared to Pso. This may indicate aberrances in cutaneous tissue homeostasis contribute to arthritis development.