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

Research output: Contribution to journalJournal article

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  • Peter C Cook
  • Lucy H Jones
  • Stephen J Jenkins
  • Thomas A Wynn
  • Judith E Allen
  • Andrew S MacDonald
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<mark>Journal publication date</mark>19/06/2012
<mark>Journal</mark>Proceedings of the National Academy of Sciences of the United States of America
Issue number25
Volume109
Number of pages6
Pages (from-to)9977-9982
Publication StatusPublished
<mark>Original language</mark>English

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-4Rα expression in the optimal induction of IFNγ 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 RELMα 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 RELMα can have on DC activation and function in the context of either bacterial or helminth pathogens.