Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-κB activation through Raf-1 and Syk
Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-κB activation through Raf-1 and Syk
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DOI：
10.1038/ni.1692
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发表时间：
2009-02-01
影响因子：
30.5
通讯作者：
Geijtenbeek, Teunis B. H.
中科院分区：
文献类型：
--
作者：
Gringhuis, Sonja I.;den Dunnen, Jeroen;Geijtenbeek, Teunis B. H.
C型凝集素dectin-1通过Syk激酶依赖的信号通路激活转录因子NF-κ B B，诱导抗真菌免疫。在这里，我们表明，在人树突状细胞上表达的dectin- 1不仅激活Syk依赖的经典NF-κ B亚基p65和c-Rel，而且还激活非经典NF-κ B亚基RelB。当被β-葡聚糖凝胶多糖或白色念珠菌刺激时，Dectin-1诱导了由丝氨酸-苏氨酸激酶Raf-1介导的第二条信号传导途径，Raf-1在NF-κ B激活时与Syk途径整合。Raf-1拮抗Syk诱导的RelB激活，通过促进螯合RelB成无活性的p65-RelB二聚体，从而改变T辅助细胞分化。因此，dectin-1激活两个独立的信号通路，一个通过Syk，一个通过Raf-1，以诱导免疫应答。
The C-type lectin dectin-1 activates the transcription factor NF-kappa 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-kappa B subunits p65 and c-Rel, but also the noncanonical NF-kappa B 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-kappa 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.