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

Cook, Peter C and Jones, Lucy H and Jenkins, Stephen J and Wynn, Thomas A and Allen, Judith E and MacDonald, Andrew S (2012) Alternatively activated dendritic cells regulate CD4+ T-cell polarization in vitro and in vivo. Proceedings of the National Academy of Sciences of the United States of America, 109 (25). pp. 9977-9982. ISSN 0027-8424

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.