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IL-4-mediated fine tuning of IL-12p70 production by human DC.

Guenova, Emmanuella, Volz, Thomas, Sauer, Karin, Kaesler, Susanne, Müller, Martin R, Wölbing, Florian, Chen, KoMing, Schwaerzler, Christoph, Brossart, Peter, Röcken, Martin and Biedermann, Tilo (2008) IL-4-mediated fine tuning of IL-12p70 production by human DC. European Journal of Immunology, 38 (11). pp. 3138-3149. ISSN 0014-2980

Abstract

IL-4 is expressed at high levels in allergic diseases and dominates the early phases of multiple acquired immune responses. However, the precise role of IL-4 during early inflammation and its impact on the differentiation of newly recruited DC precursors remains elusive. In order to characterize the impact of IL-4 on the differentiation of human DC, we investigated the role of IL-4 on the differentiation of monocytes into DC. Human DC were differentiated from peripheral blood precursors under either low or high concentrations of IL-4. We analyzed their cytokine profile and capacity to polarize T-cell differentiation. Concentrations of 5 (low) and 50 (high) ng/mL IL-4 induced two distinct types of DC. DC differentiated under low-dose IL-4 (5 ng/mL) produced almost no IL-12p70, and primed naïve CD4+ T cells allowing IL-4 secretion and Th2 induction. In contrast, DC generated under high concentrations of IL-4 (50 ng/mL) produced large amounts of IL-12p70, low IL-10 and primed naïve CD4+ T cells to become Th1 cells. Thus, we demonstrate that the Th2 cell cytokine IL-4 decisively determines the phenotype of ongoing immune responses by orchestrating the functional phenotype of newly immigrating DC precursors.

Item Type: Article
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Additional Information: archiving not allowed on institutional repository
Keywords: Cytokine; DC; Human; Inflammation; Skin
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Date Deposited: 14 Dec 2009 13:48
Last Modified: 31 Jan 2013 00:54
URI: https://oak.novartis.com/id/eprint/1471

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