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Cutting Edge: Notch Signaling Induces a Distinct Cytokine Profile in Dendritic Cells That Supports T Cell-Mediated Regulation and IL-2-Dependent IL-17 Production¹

Division of Cell and Molecular Biology, Department of Life Sciences and Centre for Integrative Systems Biology at Imperial College, Imperial College, London, United Kingdom

Recently it has been shown that dendritic cells (DC) express both Notch and Notch ligands, allowing for the possibility that Notch signaling may influence their maturation. We show that although both Jagged (Jgd) and Delta-like (DlL) ligands were able to activate the canonical Notch pathway in mouse DC, only Jgd1 could induce the production of certain cytokines. Maturation of DC via Jgd1 resulted in an entirely different maturation program from that induced through TLR (via LPS) signaling, promoting the production of high levels of IL-2 and IL-10. DC matured by Jgd1 (Jgd1-conditioned DC) promoted the survival and proliferation of CD4⁺CD25⁺ regulatory T cells that were able to suppress efficiently the proliferation of CD25^– cells. Further, CD25⁺ cells cultured with Jgd1-conditioned DC produced very high levels of IL-17 in an IL-2-dependent fashion. Our data suggest a new and important role for the Notch pathway in the regulation of the DC phenotype.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was funded by the Biotechnology and Biological Sciences Research Council and the Wellcome Trust.

² Address correspondence and reprint requests to Dr. Margaret J. Dallman, Division of Cell and Molecular Biology, Department of Life Sciences, Sir Alexander Fleming Building, Imperial College, London SW7 2AZ, U.K. E-mail address: m.dallman{at}imperial.ac.uk

³ Abbreviations used in this paper: DC, dendritic cell; DlL, Delta-like ligand; Jgd, Jagged; KO, knock-out; Treg, T regulatory cell; qRT-PCR, quantitative RT-PCR.