Th131 - Single Cell Sequencing Reveals Shared CD8+ T Cell Clones Between Skin and Synovial Tissue in Psoriatic Arthritis

Lucy Durham – King's College London; Sarah Ryan – King's College London; Giovanni Povoleri – King's College London; Elizabeth Gray – King's College London; Frances Humby – Rheumatology – Guy's and St Thomas' NHS Foundation Trust; Nora Ng – Rheumatology – Guy's and St Thomas' NHS Foundation Trust; Rosamond Nuamah – Guy's and St Thomas' NHS Foundation Trust; Kathy Fung – Guy's and St Thomas' NHS Foundation Trust; Ulrich Kadolsky; Pawan Dhami – Guy's and St Thomas' NHS Foundation Trust; Bruce Kirkham – Guy's and St Thomas' NHS Foundation Trust; Leonie Taams – King's College London

Abstract Text: IL-17 producing CD8+ tissue resident memory T-cells (TRM) are implicated in both psoriasis and psoriatic arthritis (PsA), suggesting common inflammatory processes. This raises the possibility that T-cells migrate from skin to joints to cause arthritis.

Using CITE-seq, we investigated whether the CD8+ T-cell infiltrate from paired biopsies of inflamed skin, synovial tissue +/-synovial fluid (n=4-6 PsA patients) is linked in terms of T-cell clonality and phenotype.

Synovial tissue and fluid CD8+ T-cells clustered together and had similar T-cell receptor (TCR) repertoires and therefore were pooled. There were marked differences in the frequency and phenotype of TRM cells between skin and joint: 66% skin vs. 22% synovial CD8+ T-cells resided in TRM cell clusters (defined as upregulation of ITGAE +/- CD103 protein). 94% skin and 33% synovial TRM cells resided in IL-17+ TRM clusters; whereas most (67%) synovial TRM cells resided in IL-17A-GZMK+ TRM clusters. Within each patient, select clones were present in both skin and synovium, comprising on average 7% skin and 8% synovial CD8+ TCR repertoires. These shared clones tended to fall in TRM rather than non-TRM cell clusters (odds-ratio 3.3, p< 0.0001).

In PsA, inflamed skin contains a higher proportion of CD8+ TRM cells and a stronger IL-17 signature than inflamed joints. However, CD8+ T-cells of the same clonotype are shared between both sites and shared clones have a TRM phenotype. These data indicate that the CD8+ T-cell infiltrate in skin and synovium is linked in terms of CD8+ TRM cell clonality.

Supported by MRC and NIHR-BRC at KCL/GSTT