title: Effects of interleukin (IL)-17A and IL-17F in human rheumatoid arthritis synoviocytes.
abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease where the contribution of T cells is now supported by clinical results. Among the cytokines produced by T cells, interleukin (IL)-17A (previously known as IL-17) and IL-17F constitute the signature cytokines of the newly described Th17 T helper cell subset. While the effects of IL-17A on RA synoviocytes been well described, those of IL-17F remain less studied. The present review describes the effects of IL-17A and IL-17F on synoviocytes and their contribution to RA pathogenesis. Although IL-17F is less active than IL-17A when used alone, IL-17A and IL-17F induce in synoviocytes a rather similar expression pattern in the presence of tumour necrosis factor α. They enhance their response by stabilising mRNA of cytokines and enhancing receptor expression. They increase the migration, chemokine gene expression and invasiveness of synoviocytes. They contribute to disease chronicity by inhibiting synoviocyte apoptosis. Finally, they enhance metalloprotease secretion leading to cartilage damage. These properties support the combined inhibition of IL-17A and -F to control RA inflammation and joint destruction.
authors.affiliation: Department of Clinical Immunology and Rheumatology, University of Lyon, Edouard Herriot Hospital, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Hot
authors.forename: Pierre
authors.initials: P
authors.lastname: Miossec
mesh_terms: D018501:Antirheumatic Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000502:physiology*; D053722:Receptors, Interleukin-17 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology*; D058504:Th17 Cells / Q000276:immunology
chemical_list: D018501:Antirheumatic Agents; C508717:IL17A protein, human; C440021:IL17F protein, human; D020381:Interleukin-17; D053722:Receptors, Interleukin-17