Dectin-1 interaction with tetraspanin CD37 inhibits IL-6 production
Dectin-1 interaction with tetraspanin CD37 inhibits IL-6 production
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DOI：
10.4049/jimmunol.178.1.154
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发表时间：
2007-01-01
影响因子：
4.4
通讯作者：
van Spriel, Annemiek B.
中科院分区：
文献类型：
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作者：
Meyer-Wentrup, Friederike;Figdor, Carl G.;van Spriel, Annemiek B.
C 型凝集素是模式识别受体，对于 APC 结合和摄取病原体非常重要。越来越多的证据表明，APC 中传入细胞信号的整合是通过将受体和信号分子分组为有组织的膜复合物（例如脂筏和四跨膜蛋白微域）来调节的。在这项研究中，我们证明 C 型凝集素 dectin-1 与白细胞特异性四跨膜蛋白 CD37 存在功能性相互作用。 Dectin-1 和 CD37 共定位于人类 APC 的表面。重要的是，由于 dectin-1 内化增加，CD37 缺陷 (CD37(-/-)) 小鼠的巨噬细胞表达的 dectin-1 膜水平降低。此外，将 CD37 转染至巨噬细胞系可提高内源性 dectin-1 表面表达。尽管CD37缺陷并不影响dectin-1介导的吞噬作用，但我们观察到，与野生型细胞相比，dectin-1诱导的CD37(-/-)巨噬细胞中IL-6的产生显着增加了10倍，尽管dectin-1细胞表面表达减少。重要的是，观察到的 IL-6 产量增加是 dectin-1 特异的，因为通过其他模式识别受体的信号传导在 CD37(-/-) 巨噬细胞中不受影响，并且因为使用了 dectin-1 配体凝胶多糖。总而言之，这些发现表明四跨膜蛋白 CD37 对于 APC 膜中的 dectin-1 稳定很重要，并控制 dectin-1 介导的 IL-6 产生。
C-type lectins are pattern-recognition receptors important for pathogen binding and uptake by APCs. Evidence is accumulating that integration of incoming cellular signals in APCs is regulated by grouping of receptors and signaling molecules into organized membrane complexes, such as lipid rafts and tetraspanin microdomains. In this study, we demonstrate that C-type lectin dectin-1 functionally interacts with leukocyte-specific tetraspanin CD37. Dectin-1 and CD37 colocalize on the surface of human APCs. Importantly, macrophages of CD37-deficient (CD37(-/-)) mice express decreased dectin-1 membrane levels, due to, increased dectin-1 internalization. Furthermore, transfection of CD37 into a macrophage cell line elevated endogenous dectin-1 surface expression. Although CD37 deficiency does not affect dectin-1-mediated phagocytosis, we observed a striking 10-fold increase of dectin-1-induced IL-6 production in CD37(-/-) macrophages compared with wild-type cells, despite reduced dectin-1 cell surface expression. Importantly, the observed increase in IL-6 production was specific for dectin-1, because signaling via other pattern-recognition receptors was unaffected in CD37(-/-) macrophages and because the dectin-1 ligand curdlan was used. Taken together, these findings show that tetraspanin CD37 is important for dectin-1 stabilization in APC membranes and controls dectin-1-mediated IL-6 production.