TWEAK promotes the production of Interleukin-17 in rheumatoid arthritis

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Title
TWEAK promotes the production of Interleukin-17 in rheumatoid arthritis
Author(s)
J S Park; M K Park; S Y Lee; H J Oh; M A Lim; W T Cho; E K Kim; J H Ju; Young Woo Park; S H Park; M L Cho; H Y Kim
Bibliographic Citation
Cytokine, vol. 60, no. 1, pp. 143-149
Publication Year
2012
Abstract
Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is an inflammatory cytokine that modulates several biological responses by inducing chemokines and proinflammatory cytokines. We hypothesized that TWEAK could promote secretion of IL-17, an amplifier of inflammatory arthritis. To test this, we investigated the capacity of TWEAK to induce IL-17 production in T cells via the fibroblast growth factor-inducible gene 14 (Fn14, also known as TWEAK receptor) signal pathway in rheumatoid arthritis (RA). Fn14 and IL-17 were highly expressed in arthritic tissues of collagen-induced arthritis (CIA) mice. TWEAK induced production of IL-17 alone and synergistically with lipopolysaccharide. In naive murine T cells, TWEAK promoted Th17 differentiation. The expression of Fn14 was predominant in Th17 cells. TWEAK and IL-17 concentrations were significantly higher in synovial fluid and serum in RA patients than OA patients. In addition, we identified CD4 +IL-17 +Fn14 + cells in synovium from RA patients. TWEAK promoted IL-17 production synergistically with IL-23 or IL-21 and blockade of Fn14 with Fn14-Fc suppressed Th17 differentiation. Conversely, this treatment enhanced Treg differentiation. These results suggest that TWEAK induces IL-17 production and may be a therapeutic target in the treatment of RA.
Keyword
Fibroblast growth factor inducible gene 14 (Fn14)Interleukin-17Rheumatoid arthritisTh17Tumor necrosis factor-like weak inducer of apoptosis (TWEAK)
ISSN
1043-4666
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.cyto.2012.06.285
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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