The function of interleukin 17 in the pathogenesis of rheumatoid arthritis.
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.
Paradowska
Agnieszka
A
Department of Biochemistry, Institute of Rheumatology, Warsaw, Poland. paradowska_aga@interia.pl
Maślińiski
Włodzimierz
W
Grzybowska-Kowalczyk
Agnieszka
A
Łacki
Jan
J
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020381:Interleukin-17 / Q000502:physiology*
D020381:Interleukin-17