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Lookup NU author(s): Tegan McTaggart, Jing Lim, Dr Katie SmithORCiD, Bronagh Heaney, Dr David McDonald, Dr Gill HulmeORCiD, Raf Hussain, Dr Jonathan Coxhead, Abbie Degnan, Professor John IsaacsORCiD, Dr Arthur PrattORCiD, Dr Shoba AmarnathORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Authors. Regulatory T cells (Tregs) are immune regulatory T cells that are vital for controlling inflammation. The role of Tregs in inflammatory diseases namely psoriatic arthritis (PsA) is still poorly understood. The underlying reason being a lack of robust unbiased analysis to test the immune regulatory phenotype of human Tregs. Here, we propose that checkpoint receptors can identify functional Tregs in PsA. Using unbiased BD Rhapsody single-cell analysis, we have analyzed the expression pattern of checkpoint receptors in Tregs and found that PsA Tregs are enriched in the expression of CTLA4, TIGIT, PD-1, and GITR while TIM3 was downregulated. Furthermore, PD-1+ Tregs in PsA had an increased type 1 phenotype and expressed the protease asparaginyl endopeptidase. By harnessing the PD-1 signaling pathway and inhibiting asparaginyl endopeptidase, PsA Treg function was significantly enhanced in in vitro suppressor assays. Next, we interrogated the cell interaction pathways of Tregs in PsA and found a diminished crosstalk with circulating osteoclast precursors through the CD244–CD48 coreceptor pathways. Therapeutically, PsA Treg function could be enhanced by modulating PD-1 and osteoclast interactions. Our study suggests that unconventional immune cell crosstalk with Tregs is severely diminished in PsA.
Author(s): McTaggart T, Lim JX, Smith KJ, Heaney B, McDonald D, Hulme G, Hussain R, Coxhead J, Degnan AE, Isaacs J, Pratt A, Amarnath S
Publication type: Article
Publication status: Published
Journal: Journal of Biological Chemistry
Year: 2025
Volume: 301
Issue: 1
Print publication date: 01/01/2025
Online publication date: 30/12/2024
Acceptance date: 09/12/2024
Date deposited: 07/01/2025
ISSN (print): 0021-9258
ISSN (electronic): 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology Inc.
URL: https://doi.org/10.1016/j.jbc.2024.108059
DOI: 10.1016/j.jbc.2024.108059
Data Access Statement: All the data are contained within this article. Single-cell data have been deposited at Gene Expression Omnibus under accession number GSE280319, and the code is deposited in GitHub at https://github.com/teganmct/humanscRNAseq_PSA
PubMed id: 39662827
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