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Interleukin-7: a potential factor supporting B-cell maturation in the rheumatoid arthritis synovium


1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11

 

  1. 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
  2. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK.
  3. 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.
  4. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, UK.
  5. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, UK.
  6. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, UK.
  7. 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.
  8. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK.
  9. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK.
  10. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, UK.
  11. 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
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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.

Rheumatology Article

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