Cuthbert, RJ orcid.org/0000-0002-9054-5260, Bridgewood, C, Watad, A et al. (9 more authors) (2019) Evidence that tissue resident human enthesis γδ T-cells can produce IL-17A independently of IL-23R transcript expression. Annals of the Rheumatic Diseases, 78 (11). pp. 1559-1565. ISSN 0003-4967
Abstract
Objectives: Murine models of interleukin (IL)-23-driven spondyloarthritis (SpA) have demonstrated entheseal accumulation of Î 3Î T-cells which were responsible for the majority of local IL-17A production. However, IL-23 blockers are ineffective in axial inflammation in man. This study investigated Î 3Î T-cell subsets in the normal human enthesis to explore the biology of the IL-23/17 axis. Methods: Human spinous processes entheseal soft tissue (EST) and peri-entheseal bone (PEB) were harvested during elective orthopaedic procedures. Entheseal Î 3Î T-cells were evaluated using immunohistochemistry and isolated and characterised using flow cytometry. RNA was isolated from Î 3Î T-cell subsets and analysed by qPCR. Entheseal Î 3Î T-cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, anti-CD3/28 or IL-23 and IL-17A production was measured by high-sensitivity ELISA and qPCR. Results: Entheseal Î 3Î T-cells were confirmed immunohistochemically with VÎ 1 and VÎ 2 subsets that are cytometrically defined. Transcript profiles of both cell populations suggested tissue residency and immunomodulatory status. Entheseal VÎ 2 cells expressed high relative abundance of IL-23/17-associated transcripts including IL-23R, RORC and CCR6, whereas the VÎ 1 subset almost completely lacked detectable IL-23R transcript. Following PMA stimulation IL-17A was detectable in both VÎ 1 and VÎ 2 subsets, and following CD3/CD28 stimulation both subsets showed IL-17A and IL-17F transcripts with neither transcript being detectable in the VÎ 1 subset following IL-23 stimulation. Conclusion: Spinal entheseal VÎ 1 and VÎ 2 subsets are tissue resident cells with inducible IL-17A production with evidence that the VÎ 1 subset does so independently of IL-23R expression.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Experimental Musculoskeletal Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 04 Oct 2019 11:59 |
Last Modified: | 25 Jun 2023 22:00 |
Status: | Published |
Publisher: | BMJ Publishing Group |
Identification Number: | 10.1136/annrheumdis-2019-215210 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:151804 |