Full Papers
Interleukin-7: a potential factor supporting B-cell maturation in the rheumatoid arthritis synovium
F. Ponchel1, S. Churchman2, J.J. El-Jawhari3, A.N. Burska4, P. Chambers5, E.M. Vital6, Y.M. El-Sherbiny7, E. Jones8, P.G. Conaghan9, V. Goeb10, P. Emery11
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK. mmefp@leeds.ac.uk, f.ponchel@leeds.ac.uk
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK.
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham, UK; and Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, UK.
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, UK.
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, UK.
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham, UK; and Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK.
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK.
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, UK.
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK.
CER11775
2021 Vol.39, N°2
PI 0253, PF 0262
Full Papers
PMID: 33769258 [PubMed]
Received: 18/09/2018
Accepted : 16/03/2020
In Press: 21/03/2021
Published: 09/04/2021
Abstract
OBJECTIVES:
The exact function of interleukin-7 (IL-7) in autoimmune diseases remains unclear although it is a recognised therapeutic target for cytokine blockade. Our objective was to investigate the regulation and downstream effect of IL-7 in diseased tissue from rheumatoid arthritis (RA) patients notably with respect to its function as bone turnover regulator and tissue architecture (TA) organiser.
METHODS:
Synovial tissues (fresh, frozen or xed) were obtained from our tissue bank and distributed between experiments for live cell cultures, histology, immunohistochemistry or gene expression array by qPCR.
RESULTS:
IL-7 expression in synoviocyte cultures was up-regulated by pro-in ammatory cytokines, notably IL-6. Gene expression pro ling segregated synovial biopsies based on the presence of B/plasma cells and ectopic TA. IL-7 gene expression was associated with that of several genes whose function was to support B-cell maturation in tissue with distinct B-cell aggregates (despite the lack of IL-7-Receptor expression on B-cells) as well as with ectopic germinal-like centres. IL-7 was associated with bone turnover regulation in biopsies with diffuse in ltration. A novel relationship between the IL-7 and IL-6 axis was also highlighted in human tissue.
CONCLUSIONS:
Overall, IL-7 may contribute to the maintenance of the pro-in ammatory cycle perpetuating in ammation in RA synovium. We therefore propose a novel role for IL-7 as an orchestrator of TA with an impact on B-cell maturation in relation with IL-6.
