Repository logo
 

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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Velasco-Herrera, Martin Del Castillo  ORCID logo  https://orcid.org/0000-0001-5956-0211
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.

Description

Funder: Department of Health


Funder: Wellcome Trust

Keywords

Synovial Membrane, Synovial Fluid, CD8-Positive T-Lymphocytes, Humans, Arthritis, Psoriatic, Receptors, Lymphocyte Homing, Receptors, Chemokine, Receptors, Antigen, T-Cell, alpha-beta, Gene Expression Profiling, Immunologic Memory, Single-Cell Analysis, Clonal Selection, Antigen-Mediated

Journal Title

Nature communications

Conference Name

Journal ISSN

2041-1723

Volume Title

11

Publisher

Sponsorship
Versus Arthritis (22072)