Single cell analysis of spondyloarthritis regulatory T cells identifies distinct synovial gene expression patterns and clonal fates
Regulatory T cells (Tregs) play an important role in controlling inflammation and limiting autoimmunity, but their phenotypes at inflammatory sites in human disease are poorly understood. We here analyze the single-cell transcriptome of >16,000 Tregs obtained from peripheral blood and synovial fl...
| Päätekijät: | , , , , , |
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| Aineistotyyppi: | Journal article |
| Kieli: | English |
| Julkaistu: |
Springer Nature
2021
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| _version_ | 1826269875170967552 |
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| author | Simone, D Penkava, F Ridley, A Sansom, S Al-Mossawi, M Bowness, P |
| author_facet | Simone, D Penkava, F Ridley, A Sansom, S Al-Mossawi, M Bowness, P |
| author_sort | Simone, D |
| collection | OXFORD |
| description | Regulatory T cells (Tregs) play an important role in controlling inflammation and limiting autoimmunity, but their phenotypes at inflammatory sites in human disease are poorly understood. We here analyze the single-cell transcriptome of >16,000 Tregs obtained from peripheral blood and synovial fluid of two patients with HLA-B27+ ankylosing spondylitis and three patients with psoriatic arthritis, closely related forms of inflammatory spondyloarthritis. We identify multiple Treg clusters with distinct transcriptomic profiles, including, among others, a regulatory CD8+ subset expressing cytotoxic markers/genes, and a Th17-like RORC+ Treg subset characterized by IL-10 and LAG-3 expression. Synovial Tregs show upregulation of interferon signature and TNF receptor superfamily genes, and marked clonal expansion, consistent with tissue adaptation and antigen contact respectively. Individual synovial Treg clones map to different clusters indicating cell fate divergence. Finally, we demonstrate that LAG-3 directly inhibits IL-12/23 and TNF secretion by patient-derived monocytes, a mechanism with translational potential in SpA. Our detailed characterization of Tregs at an important inflammatory site illustrates the marked specialization of Treg subpopulations.
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| first_indexed | 2024-03-06T21:32:02Z |
| format | Journal article |
| id | oxford-uuid:44fe7d10-422c-4f3d-9f96-c6ed537103b8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:32:02Z |
| publishDate | 2021 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:44fe7d10-422c-4f3d-9f96-c6ed537103b82022-03-26T15:05:08ZSingle cell analysis of spondyloarthritis regulatory T cells identifies distinct synovial gene expression patterns and clonal fatesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:44fe7d10-422c-4f3d-9f96-c6ed537103b8EnglishSymplectic ElementsSpringer Nature2021Simone, DPenkava, FRidley, ASansom, SAl-Mossawi, MBowness, PRegulatory T cells (Tregs) play an important role in controlling inflammation and limiting autoimmunity, but their phenotypes at inflammatory sites in human disease are poorly understood. We here analyze the single-cell transcriptome of >16,000 Tregs obtained from peripheral blood and synovial fluid of two patients with HLA-B27+ ankylosing spondylitis and three patients with psoriatic arthritis, closely related forms of inflammatory spondyloarthritis. We identify multiple Treg clusters with distinct transcriptomic profiles, including, among others, a regulatory CD8+ subset expressing cytotoxic markers/genes, and a Th17-like RORC+ Treg subset characterized by IL-10 and LAG-3 expression. Synovial Tregs show upregulation of interferon signature and TNF receptor superfamily genes, and marked clonal expansion, consistent with tissue adaptation and antigen contact respectively. Individual synovial Treg clones map to different clusters indicating cell fate divergence. Finally, we demonstrate that LAG-3 directly inhibits IL-12/23 and TNF secretion by patient-derived monocytes, a mechanism with translational potential in SpA. Our detailed characterization of Tregs at an important inflammatory site illustrates the marked specialization of Treg subpopulations. |
| spellingShingle | Simone, D Penkava, F Ridley, A Sansom, S Al-Mossawi, M Bowness, P Single cell analysis of spondyloarthritis regulatory T cells identifies distinct synovial gene expression patterns and clonal fates |
| title | Single cell analysis of spondyloarthritis regulatory T cells identifies distinct synovial gene expression patterns and clonal fates |
| title_full | Single cell analysis of spondyloarthritis regulatory T cells identifies distinct synovial gene expression patterns and clonal fates |
| title_fullStr | Single cell analysis of spondyloarthritis regulatory T cells identifies distinct synovial gene expression patterns and clonal fates |
| title_full_unstemmed | Single cell analysis of spondyloarthritis regulatory T cells identifies distinct synovial gene expression patterns and clonal fates |
| title_short | Single cell analysis of spondyloarthritis regulatory T cells identifies distinct synovial gene expression patterns and clonal fates |
| title_sort | single cell analysis of spondyloarthritis regulatory t cells identifies distinct synovial gene expression patterns and clonal fates |
| work_keys_str_mv | AT simoned singlecellanalysisofspondyloarthritisregulatorytcellsidentifiesdistinctsynovialgeneexpressionpatternsandclonalfates AT penkavaf singlecellanalysisofspondyloarthritisregulatorytcellsidentifiesdistinctsynovialgeneexpressionpatternsandclonalfates AT ridleya singlecellanalysisofspondyloarthritisregulatorytcellsidentifiesdistinctsynovialgeneexpressionpatternsandclonalfates AT sansoms singlecellanalysisofspondyloarthritisregulatorytcellsidentifiesdistinctsynovialgeneexpressionpatternsandclonalfates AT almossawim singlecellanalysisofspondyloarthritisregulatorytcellsidentifiesdistinctsynovialgeneexpressionpatternsandclonalfates AT bownessp singlecellanalysisofspondyloarthritisregulatorytcellsidentifiesdistinctsynovialgeneexpressionpatternsandclonalfates |