Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis
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Young, Matthew D.
Pratt, Arthur G.
Lara, Alicia Lledo
Brown, Chrysothemis C.
Croxford, Andrew L.
Isaacs, John D.
Nature Publishing Group UK
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Penkava, F., Velasco-Herrera, M. D. C., Young, M. D., Yager, N., Nwosu, L. N., Pratt, A. G., Lara, A. L., et al. (2020). Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis. Nature Communications, 11 (1) https://doi.org/10.1038/s41467-020-18513-6
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: https://doi.org/10.13039/100004440
Funder: National Institute for Health Research (NIHR) Oxford Biomedical Research Centre
Funder: St Baldrick’s Foundation
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.
Article, /631/114, /631/250/2152, /631/250/38, /631/250/256/2515, /38/91, /82/58, article
External DOI: https://doi.org/10.1038/s41467-020-18513-6
This record's URL: https://www.repository.cam.ac.uk/handle/1810/310529
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/