IL-27 Is a Key Regulator of IL-10 and IL-17 Production by Human CD4+ T Cells

Although the physiologic pathways that control regulatory T cells (Foxp3-expressing regulatory T cells, IL-10-secreting Tr1 cells) and Th17 cells in rodents have been defined, the factors that control these differentiation pathways in humans are not well understood. In this study, we show that IL-27...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2009-08, Vol.183 (4), p.2435-2443
Main Authors: Murugaiyan, Gopal, Mittal, Akanksha, Lopez-Diego, Rocio, Maier, Lisa M, Anderson, David E, Weiner, Howard L
Format: Article
Language:English
Subjects:
Autoimmune Diseases - pathology
Autoimmune Diseases - prevention & control
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
CD4-Positive T-Lymphocytes - pathology
Cell Communication - immunology
Cell Polarity - immunology
Cell Proliferation
Cells, Cultured
Coculture Techniques
Feedback, Physiological - immunology
Growth Inhibitors - physiology
Humans
Immunophenotyping
Inflammation Mediators - physiology
Interleukin-10 - biosynthesis
Interleukin-10 - metabolism
Interleukin-10 - physiology
Interleukin-17 - antagonists & inhibitors
Interleukin-17 - biosynthesis
Interleukin-17 - physiology
Interleukins - physiology
Lymphocyte Activation - immunology
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - metabolism
T-Lymphocytes, Regulatory - pathology
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Summary:Although the physiologic pathways that control regulatory T cells (Foxp3-expressing regulatory T cells, IL-10-secreting Tr1 cells) and Th17 cells in rodents have been defined, the factors that control these differentiation pathways in humans are not well understood. In this study, we show that IL-27 promotes the differentiation of IL-10-secreting Tr1 cells while inhibiting Th17 generation and molecules associated with Th17 function. Furthermore, IL-27 inhibits IL-17-polarizing cytokines on dendritic cells, which in turn decrease IL-17 secretion from T cells. Our results demonstrate that IL-27 plays a key role in human T cells by promoting IL-10-secreting Tr1 cells and inhibiting Th17 cells and thus provides a dual regulatory mechanism to control autoimmunity and tissue inflammation.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.0900568