| First Author | Diveu C | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 9 | Pages | 5748-56 |
| PubMed ID | 19380822 | Mgi Jnum | J:147706 |
| Mgi Id | MGI:3842004 | Doi | 10.4049/jimmunol.0801162 |
| Citation | Diveu C, et al. (2009) IL-27 blocks RORc expression to inhibit lineage commitment of Th17 cells. J Immunol 182(9):5748-56 |
| abstractText | IL-27 is secreted by APCs in response to inflammatory stimuli and exerts a proinflammatory Th1-enhancing activity but also has significant anti-inflammatory functions. We examined the molecular mechanism by which IL-27 regulates TGFbeta plus IL-6- or IL-23-dependent Th17 development in the mouse and human systems. IL-27 inhibited the production of IL-17A and IL-17F in naive T cells by suppressing, in a STAT1-dependent manner, the expression of the Th17-specific transcription factor RORgamma t. The in vivo significance of the role of IL-27 was addressed in delayed-type hypersensitivity response and experimental autoimmune encephalomyelitis (EAE). By generating mice deficient for the p28 subunit of IL-27, we showed that IL-27 regulated the severity of delayed-type hypersensitivity response and EAE through its effects on Th17 cells. Furthermore, up-regulation of IL-10 in the CNS, which usually occurs late after EAE onset and plays a role in the resolution of the disease, was notably absent in IL-27p28(-/-) mice. These results show that IL-27 acts as a negative regulator of the developing IL-17A response in vivo, suggesting a potential therapeutic role for IL-27 in autoimmune diseases. |
