دانلود رایگان مقاله انگلیسی نقش چندوجهی IL-21 در آرتریت روماتوئید - وایلی 2017

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disorder designated with hyperplastic synovium, bone destruction and cartilage degradation. Current therapies involve targeting major cytokines and inflammatory mediators involved in RA to alleviate the pain and provide a temporary relief. Interleukin 21 (IL-21), a recently identified cytokine is known to possess a versatile role in modulating the cells of the RA synovium. Over the past decade, the pleiotropic role of IL-21 in RA pathogenesis has been implicated in several aspects. T helper 17 (Th17) and follicular T helper cells (Tfh), being the key immunomodulators of the RA synovium secrete high amounts of IL-21 during disease progression. Several studies have provided experimental evidences elucidating the multifaceted role of IL-21 in RA disease progression. IL21 has the potential to activate T cells, B cells, monocytes/macrophages and synovial fibroblasts in RA pathogenesis through activation of JAK-STAT, MAPK and PI3K/Akt signaling pathways. Till date, therapies targeting Th17 cells and its inflammatory cytokines have been under investigation and are subjected to various clinical trials. This review showcases the function of IL-21 in RA pathogenesis and recent reports implicating its function in various immune cells, major signaling pathways and in promoting osteoclastogenesis. This article is protected by copyright.

Conclusions

IL-21, a cytokine which is majorly produced by lymphocytes (Th17, Tfh and NK cells) initiates a chain of reaction through interaction with major cells of the synovium (macrophages, dendritic cells and synovial fibroblasts) expressing IL-21R (Schematically represented in Fig. 1). Overall, IL-21 possess the potential to activate various signaling pathways including STAT-3, PI3K/Akt, MAPK and several other downstream elements resulting in aberrant cellular proliferation and inflammatory processes in RA pathogenesis (Schematically represented in This article is protected by copyright. All rights reserved  Fig. 2). The pleiotropic role of IL-21 in RA pathogenesis and disease progression makes it a major target of interest for therapeutic treatment. Our current understanding thus provides a clear picture about the relevance of IL-21 in RA pathogenesis and thus makes it an important mediator for therapeutic targeting. Several inhibitors targeted against IL-21 mediated effector molecules are under clinical trials that are undertaken to reduce the inflammatory processes in RA pathogenesis. Howbeit, therapeutic targets mediated towards IL-21/IL-21R signaling in RA pathogenesis needs to be explored in a mechanistic approach to block essential mediators required for RA disease progression.