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

• Published in: Experimental & molecular medicine 2013-10, Vol.45 (10), p.e46-e46
• Main Authors: Moon, Su-Jin, Park, Jin-Sil, Heo, Yu-Jung, Kang, Chang-Min, Kim, Eun-Kyung, Lim, Mi-Ae, Ryu, Jun-Geol, Park, Seong Jeong, Su Park, Kyung, Sung, Young-Chul, Park, Sung-Hwan, Kim, Ho-Youn, Min, Jun-Ki, Cho, Mi-La
• Format: Article
• Language: English
• Subjects: Animals; Arthritis, Experimental - drug therapy; Arthritis, Experimental - immunology; Biomedical and Life Sciences; Biomedicine; Cells, Cultured; Humans; Interleukins - immunology; Interleukins - therapeutic use; Male; Medical Biochemistry; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Molecular Medicine; Original; original-article; Stem Cells; T-Lymphocytes, Regulatory - immunology; Th17 Cells - immunology
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/emm.2013.89

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 γT 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. Rheumatoid arthritis: Immune molecule exerts anti-inflammatory effects Treatment with an immune molecule called interleukin (IL)-27 helps ameliorate the symptoms of rheumatoid arthritis (RA) and reduce inflammation, research in has shown. Mi-La Cho and colleagues at the Catholic University of Korea injected a recombinant protein containing the human IL-27 complex into mouse models of RA. The expression of another cytokine called IL-17, a known driver of RA, was subsequently reduced in the treated mice compared to controls owing to a reduction in the number