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, Lilian N. Nwosu, Arthur G. Pratt, Alicia Lledo 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 Teichmann, Paul Bowness, Sam Behjati () and M. Hussein Al-Mossawi ()
Additional contact information
Frank Penkava: Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford
Martin Del Castillo Velasco-Herrera: Wellcome Sanger Institute
Matthew D. Young: Wellcome Sanger Institute
Nicole Yager: Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford
Lilian N. Nwosu: Translational and Clinical Research Institute, Newcastle University
Arthur G. Pratt: Translational and Clinical Research Institute, Newcastle University
Alicia Lledo Lara: Wellcome Centre for Human Genetics, University of Oxford
Charlotte Guzzo: Wellcome Sanger Institute
Ash Maroof: UCB Pharma
Lira Mamanova: Wellcome Sanger Institute
Suzanne Cole: UCB Pharma
Mirjana Efremova: Wellcome Sanger Institute
Davide Simone: Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford
Andrew Filer: NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Institute of Inflammation and Ageing
Chrysothemis C. Brown: Infection, Inflammation and Rheumatology Section, UCL Great Ormond Street Institute of Child Health
Andrew L. Croxford: Idorsia Pharmaceuticals Ltd., Drug Discovery Immunology
John D. Isaacs: Translational and Clinical Research Institute, Newcastle University
Sarah Teichmann: Wellcome Sanger Institute
Paul Bowness: Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford
Sam Behjati: Wellcome Sanger Institute
M. Hussein Al-Mossawi: Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-18513-6

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