Back to Search
Start Over
IL-27 blocks RORc expression to inhibit lineage commitment of Th17 cells
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 182(9)
- Publication Year :
- 2009
-
Abstract
- 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 TGFβ 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 RORγt. 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.
- Subjects :
- Encephalomyelitis, Autoimmune, Experimental
Receptors, Retinoic Acid
Encephalomyelitis
Immunology
Biology
Proinflammatory cytokine
Mice
RAR-related orphan receptor gamma
In vivo
medicine
Immunology and Allergy
Animals
Humans
Cell Lineage
Genetic Predisposition to Disease
Interleukin 27
Transcription factor
Cells, Cultured
Mice, Knockout
Receptors, Thyroid Hormone
Interleukins
Experimental autoimmune encephalomyelitis
Interleukin-17
Cell Differentiation
T-Lymphocytes, Helper-Inducer
Nuclear Receptor Subfamily 1, Group F, Member 3
medicine.disease
Growth Inhibitors
Mice, Inbred C57BL
Protein Subunits
Gene Expression Regulation
Experimental pathology
Subjects
Details
- ISSN :
- 15506606
- Volume :
- 182
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....bc82777ee66260ec3556816dac7878dd