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.

cAMP-responsive Element Modulator α (CREMα) Suppresses IL-17F Protein Expression in T Lymphocytes from Patients with Systemic Lupus Erythematosus (SLE)

“…The namesake cytokine IL-17A was first discovered as "cytotoxic T lymphocyte-associated antigen 8" but has been documented to be expressed by multiple cells, including immune cells, fibroblasts, and synoviocytes (2,3,15). Over the past decade, the IL-17 cytokine family has been expanded by five new members, IL-17B through IL-17F, with IL-17A and IL-17F being the most closely related and well studied (2).…”

“…Increased expression of IL-17A has been documented in SLE (11)(12)(13)(14), rheumatoid arthritis (15), psoriasis (16), and multiple sclerosis (17,18). Recently, we demonstrated the involvement of the transcriptional regulatory factor cAMP-responsive element modulator ␣ (CREM␣) in the induction of IL-17A expression in SLE T lymphocytes (14).…”

Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry

“…T cells in RA pathophysiology can be mediated through Th1 effector functions, Th17 activity or induction of anti-citrullinated protein antibodies, leading to bone and cartilage destruction. 20 It is now thought that 2 signals from the antigen-presenting cell (APC) are needed to activate T cells. The first signal arises when antigenic peptides are presented on the antigen-presenting cell through the major histocompatibility complex (MHC), which is antigen specific.…”

A CD46 transgenic mouse model for studying the histopathology of arthritis caused by subcutaneous infection with Streptococcus dysgalactiae subspecies equisimilis

“…RANKL is the primary mediator of osteoclast differentiation, activation and survival (Yasuda et al, 1998b). IL-17A, in contrast, acts upstream from IL-6 and synergizes with TNF-a to promote inflammation and bone turnover in rheumatoid arthritis (Hot & Miossec, 2011;Lubberts, 2008Lubberts, , 2010. IL-17A suppresses the expression of bone resorption-related proteinases and osteoclast differentiation (osteoclast precursors into osteoclasts) (Kitami et al, 2010).…”