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

作者：Cook Peter C; Jones Lucy H; Jenkins Stephen J; Wynn Thomas A; Allen Judith E; MacDonald Andrew S^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(25): 9977-9982.

DOI：10.1073/pnas.1121231109

• antigen presenting cells
• T lymphocytes
• innate immunity
• adaptive immunity

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 alpha expression in the optimal induction of IFN gamma 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 alpha 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 alpha can have on DC activation and function in the context of either bacterial or helminth pathogens.

• 出版日期2012-6-19