Article abstract
Nature Immunology 10, 203 - 213 (2009)
Published online: 4 January 2009 | doi:10.1038/ni.1692
Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-
B activation through Raf-1 and Syk
Sonja I Gringhuis1,2, Jeroen den Dunnen1,2, Manja Litjens1, Michiel van der Vlist1, Brigitte Wevers1, Sven C M Bruijns1 & Teunis B H Geijtenbeek1
Abstract
The C-type lectin dectin-1 activates the transcription factor NF-
B through a Syk kinase–dependent signaling pathway to induce antifungal immunity. Here we show that dectin-1 expressed on human dendritic cells activates not only the Syk-dependent canonical NF-B subunits p65 and c-Rel, but also the noncanonical NF-B subunit RelB. Dectin-1, when stimulated by the 
-glucan curdlan or by Candida albicans, induced a second signaling pathway mediated by the serine-threonine kinase Raf-1, which integrated with the Syk pathway at the point of NF-B activation. Raf-1 antagonized Syk-induced RelB activation by promoting sequestration of RelB into inactive p65-RelB dimers, thereby altering T helper cell differentiation. Thus, dectin-1 activates two independent signaling pathways, one through Syk and one through Raf-1, to induce immune responses.
- Department of Molecular Cell Biology and Immunology, Vrije University Medical Center, 1007 MC Amsterdam, The Netherlands.
- These authors contributed equally to this work.
Correspondence to: Teunis B H Geijtenbeek1 e-mail: t.geijtenbeek@vumc.nl
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