Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis

Nat Commun. 2020 Sep 21;11(1):4767. doi: 10.1038/s41467-020-18513-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Psoriatic / blood
  • Arthritis, Psoriatic / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Clonal Selection, Antigen-Mediated*
  • Gene Expression Profiling
  • Humans
  • Immunologic Memory
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Receptors, Chemokine / metabolism
  • Receptors, Lymphocyte Homing / genetics
  • Receptors, Lymphocyte Homing / metabolism*
  • Single-Cell Analysis
  • Synovial Fluid / immunology*
  • Synovial Membrane / immunology

Substances

  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Chemokine
  • Receptors, Lymphocyte Homing