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

Penkava, Frank, Velasco-Herrera, Martin Del Castillo, Young, Matthew D, Yager, Nicole, Nwosu, Lilian N, Pratt, Arthur G, Lara, Alicia Lledo, Guzzo, Charlotte, Maroof, Ash, Mamanova, Lira, Cole, Suzanne, Efremova, Mirjana, Simone, Davide, Filer, Andrew, Brown, Chrysothemis C, Croxford, Andrew L, Isaacs, John D, Teichmann, Sarah, Bowness, Paul, Behjati, Sam and Hussein Al-Mossawi, M (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). p. 4767. ISSN 2041-1723. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

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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.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: QV Pharmacology
QW Microbiology. Immunology
WE Musculoskeletal. Orthopaedics
Divisions: Planned IP Care > Trauma and Orthopaedics
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Depositing User: Jamie Edgar
Date Deposited: 09 Oct 2020 13:56
Last Modified: 09 Oct 2020 13:56
URI: http://www.repository.uhblibrary.co.uk/id/eprint/3527

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