The function of interleukin 17 in the pathogenesis of rheumatoid arthritis

Abstract

Interleukin (IL)-17 is a 30- to 35-kDa homodimeric polypeptide cytokine cloned in 1993 and originally named cytotoxic T lymphocyte-associated antigen-8 (CTLA-8). Sequencing the human genome resulted in the discovery of an additional five members of the IL-17 family that were consecutively named IL-17B to IL-17F. IL-17A is exclusively produced by a newly identified CD4+ T-helper subset that was recently named Th17. Differentiation of these cells from naive CD4+ T cells requires both TGF-beta and IL-6. IL-15 and, especially, IL-23 are required for these cells' survival and efficient IL-17 production. IL-17 binding to an IL-17 receptor expressed on epithelial, endothelial, and fibroblastic stromal cells triggers the activation of transcription factor NF-kappaB and mitogen-activated protein kinase (p-38), which in turn results in the secretion of IL-1, TNF-alpha, IL-6, IL-8, or prostaglandin E2. The IL-17 family plays a key role in the regulation of immune and inflammatory response, in the homeostasis of several tissues, and the progression of autoimmune diseases. In addition, IL-17 exerts synergistic effects with TNF-alpha and IL-1 in the induction of joint inflammation and cartilage and joint destruction. Given these properties, it is not surprising that in certain pathological conditions, for example rheumatoid arthritis, Th17 cells emerge as a new pathological cell type that, by IL-17 production and release, contributes to their pathogeneses.

Role of interleukin-23 as a biomarker in rheumatoid arthritis patients and its correlation with disease activity

“…The autoimmune response in RA is initiated by the activation of antigen-specific T cells [15]. Th17 cells are a distinct subset of T helper cells that play a role in the activation of the immune system by stimulating pro-inflammatory cytokine production via IL-17 [16].…”

Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications

“…It acts on a variety of cells involving the development of autoimmunity, inflammation, and tumors. IL-17A and IL-17F genes share the highest degree of homology of about 50%, while the others have only 16%-30% of identity at the primary sequence level [126,[129][130][131][132] . IL-17F (OMIM 606496) is a novel proinflammatory cytokine which induces the expression of cytokines and chemokines.…”

Pathogenic Role of Interlukin-23(IL-23) in Rheumatoid Arthritis Patients; its Relation to Disease Activity

“…The autoimmune response in RA is initiated by the activation of antigen-specific T cells. 15 Th17 cells are a distinct subset of T helper cells that play a role in the activation of the immune system by stimulating proinflammatory cytokine production via IL-17. 16 Results from studies using different arthritis models have demonstrated that IL-17-producing T-cells are the dominant cell type in the development of arthritis.…”