Impact of simultaneous neutralization of IL-17A and treatment with recombinant IL-2 on Th17-Treg cell population in S.aureus induced septic arthritis. (February 2020)

• Record Type: Journal Article
• Authors: Dey, Ipsita; Bishayi, Biswadev
• Is Part Of: Microbial pathogenesis. Volume 139(2020)
• Publication Date: 2020-02
• Subjects: IL-17 antibody -- IL-2 -- S. aureus arthritis -- T helper 17 -- T regulatory cells; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2019.103903
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: The contribution of Th17 and Treg in the pathogenesis of septic arthritis is well known. The imbalance of Th17/Treg ratio, especially the skewed CD4 + T cell differentiation towards pathogenic Th17 lineage is a major reason that mediates bone damage through one of its prime cytokine member IL-17A. The neutralization of released IL-17A, as well as exogenous administration of IL-2 at a lower dose, was seen to be potent in dampening the inflammatory response in many cases. Interestingly the effect of IL-17A neutralization to limit IL-17 mediated inflammation and induction of Tregs by the administration of IL-2 has not been studied in experimental arthritis. So in this study, we have treated arthritic mice with IL-17A Ab and recombinant mouse IL-2 either alone or in combination at 3, 9 and 15 days post-infection. We have found a marked decrease in Th17 cell population and their related pro-inflammatory cytokine levels at 15DPI in arthritic mice after IL-17 neutralization. An increased Treg cell population was also observed in mice after application of rIL-2 with a significantly heightened TGF-β level in serum and synovial joints compared to the untreated one. However, in the case of combination therapy of IL-17A Ab and rIL-2 we have observed a beneficial effect in ameliorating the disease outcome as the arthritic index was decreased maximally at 15DPI with a significant reduction of arthritis compared to individual treatment. Overall the inflammatory microenvironment was counterbalanced most effectively in combination treatment by lowering the Th17/Treg ratio and their related cytokines that resulted in reducing the immunopathogenesis of the destructive arthritis. Highlights: Imbalance of Th17/Treg leads to inflammation in S.aureus induced arthritis. IL-17 antibody and IL-2 treatment seem to improve various inflammatory outcomes. Arthritic animals were treated with IL-17 Ab and/or IL-2. Th17/Treg ratio and their related cytokines were studied from blood and tissues. Combination treatment of IL-17 Ab and IL-2 lowered Th17/Treg ratio most effectively.