Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-020-18513-6
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Funding
- Kennedy Trust Studentship
- Academy of Medical Sciences Grant [SGL018\1006]
- Oxford-UCB Prize fellowship
- Wellcome
- St. Baldrick's Foundation
- National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC)
- NIHR Birmingham BRC at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham
- National Institute of Health Research (NIHR) Newcastle Biomedical Research Centre at Newcastle Hospitals Foundation Trust and Newcastle University
- Versus Arthritis Research into Inflammatory Arthritis Centre [22072]
- MRC [G1001518] Funding Source: UKRI
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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. Psoriatic arthritis (PsA) commonly affects patients with skin psoriasis, but its pathogenesis is still unclear. Here the authors use two types of single-cells data, mass cytometry and RNA sequencing, to describe the expansion and diversity of synovial, but not peripheral blood, CD8 T cells from PsA patients to provide a molecular immune landscape for PsA.
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