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

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Velasco-Herrera, Martin Del Castillo  ORCID logo
Young, Matthew D. 
Yager, Nicole 


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.


Funder: Kennedy Trust studentship

Funder: Oxford-UCB Prize Fellowship

Funder: National Institute of Health Research (NIHR) Newcastle Biomedical Research Centre at Newcastle Hospitals Foundation Trust and Newcastle University and Versus Arthritis Research into Inflammatory Arthritis Centre; ref. 22072).

Funder: NIHR Birmingham BRC at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham

Funder: Wellcome Trust (Wellcome); doi:

Funder: National Institute for Health Research (NIHR) Oxford Biomedical Research Centre

Funder: St Baldrick’s Foundation


Article, /631/114, /631/250/2152, /631/250/38, /631/250/256/2515, /38/91, /82/58, article

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Nature Communications

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Nature Publishing Group UK