Single-cell characterisation of tissue homing CD4 + and CD8 + T cell clones in immune-mediated refractory arthritis

Immune-mediated arthritis is a group of autoinflammatory diseases, where the patient's own immune system attacks and destroys synovial joints. Sustained remission is not always achieved with available immunosuppressive treatments, warranting more detailed studies of T cell responses that perpet...

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Bibliographic Details
Published in:Molecular medicine (Cambridge, Mass.) Mass.), 2024-04, Vol.30 (1), p.48-48, Article 48
Main Authors: Bhattacharya, Dipabarna, Theodoropoulos, Jason, Nurmi, Katariina, Juutilainen, Timo, Eklund, Kari K, Koivuniemi, Riitta, Kelkka, Tiina, Mustjoki, Satu, Lönnberg, Tapio
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Arthritis
Arthritis - metabolism
Arthritis - pathology
Autoimmunity
CD4-Positive T-Lymphocytes - metabolism
CD8-Positive T-Lymphocytes - metabolism
Clone Cells
Humans
scRNA-seq
Short Report
Synovial Membrane
T cell
TCR-seq
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Summary:Immune-mediated arthritis is a group of autoinflammatory diseases, where the patient's own immune system attacks and destroys synovial joints. Sustained remission is not always achieved with available immunosuppressive treatments, warranting more detailed studies of T cell responses that perpetuate synovial inflammation in treatment-refractory patients. In this study, we investigated CD4 + and CD8 + T lymphocytes from the synovial tissue and peripheral blood of patients with treatment-resistant immune-mediated arthritis using paired single-cell RNA and TCR-sequencing. To gain insights into the trafficking of clonal families, we compared the phenotypes of clones with the exact same TCRß amino acid sequence between the two tissues. Our results show that both CD4 + and CD8 + T cells display a more activated and inflamed phenotype in the synovial tissue compared to peripheral blood both at the population level and within individual T cell families. Furthermore, we found that both cell subtypes exhibited clonal expansion in the synovial tissue. Our findings suggest that the local environment in the synovium drives the proliferation of activated cytotoxic T cells, and both CD4 + and CD8 + T cells may contribute to tissue destruction and disease pathogenesis.
ISSN:1528-3658
1076-1551
1528-3658
DOI:10.1186/s10020-024-00802-1