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Alternatively activated dendritic cells regulate CD4+ T-cell polarization in vitro and in vivo.


ABSTRACT: Interleukin-4 is a cytokine widely known for its role in CD4(+) T cell polarization and its ability to alternatively activate macrophage populations. In contrast, the impact of IL-4 on the activation and function of dendritic cells (DCs) is poorly understood. We report here that DCs respond to IL-4 both in vitro and in vivo by expression of multiple alternative activation markers with a different expression pattern to that of macrophages. We further demonstrate a central role for DC IL-4R? expression in the optimal induction of IFN? responses in vivo in both Th1 and Th2 settings, through a feedback loop in which IL-4 promotes DC secretion of IL-12. Finally, we reveal a central role for RELM? during T-cell priming, establishing that its expression by DCs is critical for optimal IL-10 and IL-13 promotion in vitro and in vivo. Together, these data highlight the significant impact that IL-4 and RELM? can have on DC activation and function in the context of either bacterial or helminth pathogens.

SUBMITTER: Cook PC 

PROVIDER: S-EPMC3382483 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Alternatively activated dendritic cells regulate CD4+ T-cell polarization in vitro and in vivo.

Cook Peter C PC   Jones Lucy H LH   Jenkins Stephen J SJ   Wynn Thomas A TA   Allen Judith E JE   MacDonald Andrew S AS  

Proceedings of the National Academy of Sciences of the United States of America 20120601 25


Interleukin-4 is a cytokine widely known for its role in CD4(+) T cell polarization and its ability to alternatively activate macrophage populations. In contrast, the impact of IL-4 on the activation and function of dendritic cells (DCs) is poorly understood. We report here that DCs respond to IL-4 both in vitro and in vivo by expression of multiple alternative activation markers with a different expression pattern to that of macrophages. We further demonstrate a central role for DC IL-4Rα expre  ...[more]

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