Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis
Frank Penkava, Martin Del Castillo Velasco‐Herrera, Matthew D. Young, Nicole Yager, L.N. Nwosu, Arthur G. Pratt, Alicia Lledó Lara, Charlotte Guzzo, Ash Maroof, Lira Mamanova, Suzanne Cole, Mirjana Efremova, Davide Simone, Andrew Filer, Chrysothemis C. Brown, Andrew L. Croxford, John D. Isaacs, Sarah A. Teichmann, Paul Bowness, Sam Behjati, Hussein Al‐Mossawi
Abstract
Psoriatic arthritis (PsA) is a debilitating immune-mediated inflammatory arthritis of unknown pathogenesis commonly affecting patients with skin psoriasis. Here we use complementary single-cell approaches to study leukocytes from PsA joints. Mass cytometry demonstrates a 3-fold expansion of memory CD8 T cells in the joints of PsA patients compared to peripheral blood. Meanwhile, droplet-based and plate-based single-cell RNA sequencing of paired T cell receptor alpha and beta chain sequences show pronounced CD8 T cell clonal expansions within the joints. Transcriptome analyses find these expanded synovial CD8 T cells to express cycling, activation, tissue-homing and tissue residency markers. T cell receptor sequence comparison between patients identifies clonal convergence. Finally, chemokine receptor CXCR3 is upregulated in the expanded synovial CD8 T cells, while two CXCR3 ligands, CXCL9 and CXCL10, are elevated in PsA synovial fluid. Our data thus provide a quantitative molecular insight into the cellular immune landscape of psoriatic arthritis.