Substantive Similarities Between Synovial Fluid and Synovial Tissue T cells in Inflammatory Arthritis Via Single-Cell RNA and T Cell Receptor Sequencing.

Autor: Durham LE; King's College London, London, United Kingdom., Humby FC; Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Ng N; Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Ryan S; King's College London, London, United Kingdom., Nuamah R; Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Fung K; Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Kallayil AM; Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Dhami P; Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Kirkham BW; Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Taams LS; King's College London, London, United Kingdom.
Jazyk: angličtina
Zdroj: Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2024 Nov; Vol. 76 (11), pp. 1594-1601. Date of Electronic Publication: 2024 Aug 27.
DOI: 10.1002/art.42949
Abstrakt: Objective: Synovial fluid (SF)-derived T cells are frequently studied as a proxy for investigating the synovial tissue (ST) T cell infiltrate in inflammatory arthritis. However, because ST is the primary site of inflammatory activity, there is debate as to whether SF provides a true reflection of the ST T cell population.
Methods: In this study, we used single-cell RNA sequencing paired with single-cell T cell receptor (TCR) sequencing to directly compare memory T cells from paired samples of SF and ST from six patients with inflammatory arthritis to investigate their similarity in terms of TCR repertoire and T cell subset composition.
Results: The TCR repertoires of SF and ST T cells were strikingly similar, particularly for CD8+ T cells. A median of 49% of the total CD8+ TCR repertoire in SF was shared with ST, compared with 20% shared with blood. Similarly, 47% of the ST CD8+ TCR repertoire was shared with SF compared to 25% with blood. Furthermore, once the effect of collagenase digestion on gene expression by ST T cells had been accounted for, the frequencies of specific CD8+ and CD4+ T cell subsets were, in general, similar in SF and ST and were distinct from blood.
Conclusion: Our results suggest that T cells migrate and equilibrate between the SF and ST and maintain similar phenotypes in both sites. We conclude that SF is an appropriate proxy for investigating the T cell infiltrate in inflamed synovium, particularly in terms of investigating the TCR repertoire.
(© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
Databáze: MEDLINE
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