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In vivo action of IL-27: reciprocal regulation of Th17 and Treg cells in collagen-induced arthritis SCIE SCOPUS KCI

Title
In vivo action of IL-27: reciprocal regulation of Th17 and Treg cells in collagen-induced arthritis
Authors
Moon, SJPark, JSHeo, YJKang, CMKim, EKLim, MARyu, JGPark, SJPark, KSSung, YCPark, SHKim, HYMin, JKCho, ML
Date Issued
2013-10
Publisher
NATURE PUBLISHING GROUP
Abstract
Interleukin (IL)-27 is a novel cytokine of the IL-6/IL-12 family that has been reported to be involved in the pathogenesis of autoimmune diseases and has a pivotal role as both a pro-and anti-inflammatory cytokine. We investigated the in vivo effects of IL-27 on arthritis severity in a murine collagen-induced arthritis (CIA) model and its mechanism of action regarding control of regulatory T (Tregs) and IL-17-producing T helper 17 (Th17) cells. IL-27-Fc-treated CIA mice showed a lower severity of arthritis. IL-17 expression in the spleens was significantly decreased in IL-27-Fc-treated CIA mice compared with that in the CIA model. The Th17 population was decreased in the spleens of IL-27-Fc-treated CIA mice, whereas the CD4(+)CD25(+)Foxp(3+) Treg population increased. In vitro studies revealed that IL-27 inhibited IL-17 production in murine CD4(+) T cells, and the effect was associated with retinoic acid-related orphan receptor gamma T and signal transducer and activator of transcription 3 inhibition. In contrast, fluorescein isothiocyanate-labeled forkhead box P3 (Foxp3) and IL-10 were profoundly augmented by IL-27 treatment. Regarding the suppressive capacity of Treg cells, the proportions of CTLA-4(+) (cytotoxic T-lymphocyte antigen 4), PD-1(+) (programmed cell death protein 1) and GITR(+) (glucocorticoid-induced tumor necrosis factor receptor) Tregs increased in the spleens of IL-27-Fc-treated CIA mice. Furthermore, in vitro differentiated Treg cells with IL-27 exerted a more suppressive capacity on T-cell proliferation. We found that IL-27 acts as a reciprocal regulator of the Th17 and Treg populations in CD4(+) cells isolated from healthy human peripheral blood mononuclear cells (PBMCs), as well as from humans with rheumatoid arthritis (RA) PBMCs. Our study suggests that IL-27 has the potential to ameliorate overwhelming inflammation in patients with RA through a reciprocal regulation of Th17 and Treg cells.
Keywords
collagen-induced arthritis; interleukin-27; interleukin-17-producing T cells; regulatory T cells; rheumatoid arthritis; TNF-ALPHA THERAPY; PATHOGENIC T-CELL; RHEUMATOID-ARTHRITIS; DESTRUCTIVE ARTHRITIS; TGF-BETA; AUTOIMMUNE ENCEPHALOMYELITIS; INTERFERON-GAMMA; SYNOVIAL-FLUID; ANIMAL-MODELS; INFLAMMATION
URI
https://oasis.postech.ac.kr/handle/2014.oak/10207
DOI
10.1038/EMM.2013.89
ISSN
1226-3613
Article Type
Article
Citation
EXPERIMENTAL AND MOLECULAR MEDICINE, vol. 45, 2013-10
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성영철SUNG, YOUNG CHUL
Dept of Life Sciences
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