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

S.I. Gringhuis, J. den Dunnen, M. Litjens, M. van der Vlist, B. Wevers, S.C.M. Bruijns, T.B.H. Geijtenbeek

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336 Citations (Scopus)

Abstract

The C-type lectin dectin-1 activates the transcription factor NF-kappaB 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-kappaB subunits p65 and c-Rel, but also the noncanonical NF-kappaB subunit RelB. Dectin-1, when stimulated by the beta-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-kappaB 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
Original languageUndefined/Unknown
Pages (from-to)203-213
JournalNature immunology
Volume10
Issue number2
DOIs
Publication statusPublished - 2009

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