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Nature Immunology 10, 203–213 (1 February 2009) | doi:10.1038/ni.1692

Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-|[kappa]|B activation through Raf-1 and Syk

Sonja I Gringhuis , Jeroen den Dunnen , Manja Litjens , Michiel van der Vlist , Brigitte Wevers , Sven C M Bruijns & Teunis B H Geijtenbeek

The C-type lectin dectin-1 activates the transcription factor NF-κB 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-κB subunits p65 and c-Rel, but also the noncanonical NF-κB subunit RelB. Dectin-1, when stimulated by the β-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-κB 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.