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

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openAccess

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Journal Title

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Volume Title

A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Date

2024-04-09

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Mcode

Degree programme

Language

en

Pages

14

Series

Molecular Medicine, Volume 30, issue 1, pp. 1-14

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

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Publisher Copyright: © The Author(s) 2024.

Keywords

Arthritis, Autoimmunity, scRNA-seq, T cell, TCR-seq

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Citation

Bhattacharya, D, Theodoropoulos, J, Nurmi, K, Juutilainen, T, Eklund, K K, Koivuniemi, R, Kelkka, T, Mustjoki, S & Lönnberg, T 2024, ' Single-cell characterisation of tissue homing CD4 + and CD8 + T cell clones in immune-mediated refractory arthritis ', Molecular Medicine, vol. 30, no. 1, 48, pp. 1-14 . https://doi.org/10.1186/s10020-024-00802-1