Cuthbert, RJ orcid.org/0000-0002-9054-5260, Fragkakis, EM, Dunsmuir, R et al. (7 more authors) (2017) Group 3 Innate Lymphoid Cells in Human Enthesis. Arthritis & Rheumatology, 69 (9). pp. 1816-1822. ISSN 2326-5191
Abstract
Objective
Group 3 innate lymphoid cells (ILC3s) play a pivotal role in barrier tissues such as the gut and the skin, two important sites of disease in spondyloarthropathy (SpA). It was investigated whether normal and injured human enthesis, the key target tissue in early SpA, harboured ILC3s in entheseal soft tissue (EST) and adjacent peri-entheseal bone (PEB).
Methods
Interspinous ligament and spinous process bone was collected from donors with no systemic inflammatory disease, enzymatically digested and immunophenotyped. The immunological profile of entheseal cells was examined and the transcriptional profile of sorted ILC3s was compared to those isolated from SpA synovial fluid. To assess the ability of entheseal tissue to produce IL-17 and IL-22 entheseal digests were stimulated with IL-23 and IL-1β. Osteoarthritic and ruptured Achilles tissue was examined histologically.
Results
Compared to peripheral blood, human EST had a higher proportion of ILCs (p=0.008), EST and PEB both had a higher proportion of NKp44+ ILC3s (p=0.001 and p=0.043). RORγt, STAT3 and IL-23R transcript expression validated the entheseal ILC3 phenotype. Cytokine transcript expression was similar in ILC3s isolated from enthesis and SpA synovial fluid. Normal entheseal digests stimulated with IL-23/IL-1β upregulated IL17A transcript and histological examination of injured/damaged entheses showed RORγt expressing cells.
Conclusion
This work shows that human enthesis harbours a resident population of ILC3s, with the potential to participate in spondyloarthropathy pathogenesis. This article is protected by copyright. All rights reserved.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2017 Wiley. This is the peer reviewed version of the following article: Cuthbert, RJ, Fragkakis, EM, Dunsmuir, R et al. (7 more authors) (2017) Human Enthesis Group 3 Innate Lymphoid Cells. Arthritis & Rheumatology , which has been published in final form at https://dx.doi.org/10.1002/art.40150. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
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) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Orthopaedics (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 09 Jun 2017 09:16 |
Last Modified: | 07 Nov 2019 16:16 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/art.40150 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:117476 |