Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis.
Arthritis, Psoriatic
/ blood
CD8-Positive T-Lymphocytes
/ immunology
Clonal Selection, Antigen-Mediated
Gene Expression Profiling
Humans
Immunologic Memory
Receptors, Antigen, T-Cell, alpha-beta
/ genetics
Receptors, Chemokine
/ metabolism
Receptors, Lymphocyte Homing
/ genetics
Single-Cell Analysis
Synovial Fluid
/ immunology
Synovial Membrane
/ immunology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 09 2020
21 09 2020
Historique:
received:
06
08
2019
accepted:
27
08
2020
entrez:
22
9
2020
pubmed:
23
9
2020
medline:
9
10
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32958743
doi: 10.1038/s41467-020-18513-6
pii: 10.1038/s41467-020-18513-6
pmc: PMC7505844
doi:
Substances chimiques
Receptors, Antigen, T-Cell, alpha-beta
0
Receptors, Chemokine
0
Receptors, Lymphocyte Homing
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4767Subventions
Organisme : Medical Research Council
ID : G1001518
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P020941/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 201483/Z/16/Z
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Versus Arthritis
ID : 22072
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
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