Alternatively activated dendritic cells regulate CD4+ T-cell polarization in vitro and in vivo.
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.
Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, School of Biological Sciences,  University of Edinburgh, Edinburgh EH9 3JT, Scotland,  United Kingdom.
Peter C
PC
Cook
Lucy H
LH
Jones
Stephen J
SJ
Jenkins
Thomas A
TA
Wynn
Judith E
JE
Allen
Andrew S
AS
MacDonald
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016764:Cell Polarity; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D008262:Macrophage Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction
D016207:Cytokines