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

Abstract : Objective 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 fixed) 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-inflammatory cytokines, notably IL-6. Gene expression profiling 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 infiltration. A novel relationship between the IL-7 and IL-6 axis was also highlighted in human tissue. Conclusion Overall, IL-7 may contribute to the maintenance of the pro-inflammatory cycle perpetuating inflammation 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.