Bridgewood, C, Watad, A, Russell, T et al. (10 more authors) (2019) Identification of myeloid cells in the human enthesis as the main source of local IL-23 production. Annals of the rheumatic diseases, 78 (7). pp. 929-933. ISSN 0003-4967
Abstract
Objective We investigated whether the normal human spinal enthesis contained resident myeloid cell populations, capable of producing pivotal proinflammatory cytokines including tumour necrosis factor (TNF) and interleukin (IL)-23 and determined whether these could be modified by PDE4 inhibition.
Methods Normal human enthesis soft tissue (ST) and adjacent perientheseal bone (PEB) (n=15) were evaluated using immunohistochemistry (IHC), digested for myeloid cell phenotyping, sorted and stimulated with different adjuvants (lipopolysaccharide and mannan). Stimulated enthesis fractions were analysed for inducible production of spondyloarthropathy disease-relevant mediators (IL-23 full protein, TNF, IL-1β and CCL20). Myeloid populations were also compared with matched blood populations for further mRNA analysis and the effect of PDE4 inhibition was assessed.
Results A myeloid cell population (CD45+ HLADR+ CD14+ CD11c+) phenotype was isolated from both the ST and adjacent PEB and termed ‘CD14+ myeloid cells’ with tissue localisation confirmed by CD14+ IHC. The CD14− fraction contained a CD123+ HLADR+ CD11c− cell population (plasmacytoid dendritic cells). The CD14+ population was the dominant entheseal producer of IL-23, IL-1β, TNF and CCL20. IL-23 and TNF from the CD14+ population could be downregulated by a PDE4I and other agents (histamine and 8-Bromo-cAMP) which elevate cAMP. Entheseal CD14+ cells had a broadly similar gene expression profile to the corresponding CD14+ population from matched blood but showed significantly lower CCR2 gene expression.
Conclusions The human enthesis contains a CD14+ myeloid population that produces most of the inducible IL-23, IL-1β, TNF and CCL20. This population has similar gene expression profile to the matched blood CD14+ population.
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/. |
Keywords: | IL-23; enthesis; myeloid cell; pde4 inhibitors; spondyloarthritis |
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) |
Funding Information: | Funder Grant number Novartis Pharmaceuticals UK Ltd Not Known |
Depositing User: | Symplectic Publications |
Date Deposited: | 08 May 2019 11:18 |
Last Modified: | 25 Jun 2023 21:48 |
Status: | Published |
Publisher: | BMJ Publishing Group |
Identification Number: | 10.1136/annrheumdis-2018-214944 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:145746 |