In vivo action of IL-27: reciprocal regulation of Th17 and Treg cells in collagen-induced arthritis.
- Author:
Su Jin MOON
1
;
Jin Sil PARK
;
Yu Jung HEO
;
Chang Min KANG
;
Eun Kyung KIM
;
Mi Ae LIM
;
Jun Geol RYU
;
Seong Jeong PARK
;
Kyung Su PARK
;
Young Chul SUNG
;
Sung Hwan PARK
;
Ho Youn KIM
;
Jun Ki MIN
;
Mi La CHO
Author Information
1. Bucheon St Mary's Hospital, Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Bucheon City, Gyeonggi-do, Republic of Korea. min6403@catholic.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
collagen-induced arthritis;
interleukin-27;
interleukin-17-producing T cells;
regulatory T cells;
rheumatoid arthritis
- MeSH:
Animals;
Arthritis, Experimental/*drug therapy/immunology;
Cells, Cultured;
Humans;
Interleukins/immunology/*therapeutic use;
Male;
Mice;
Mice, Inbred C57BL;
Mice, Inbred DBA;
T-Lymphocytes, Regulatory/*immunology;
Th17 Cells/*immunology
- From:Experimental & Molecular Medicine
2013;45(10):e46-
- CountryRepublic of Korea
- Language:English
-
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+Foxp3+ 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 gammaT 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.
