Requirement of phospholipase C‐γ2 (PLCγ2) for Dectin‐1‐induced antigen presentation and induction of TH1/TH17 polarization
Requirement of phospholipase C‐γ2 (PLCγ2) for Dectin‐1‐induced antigen presentation and induction of TH1/TH17 polarization
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Dectin-1 诱导的抗原呈递和 TH1/TH17 极化诱导需要磷脂酶 C-γ2 (PLCγ2)
DOI：
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发表时间：
2009
影响因子：
5.4
通讯作者：
M. Colonna
中科院分区：
文献类型：
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作者：
Ilaria Tassi;M. Cella;I. Castro;S. Gilfillan;W. Khan;M. Colonna
DC通过一系列被称为PRR的受体识别微生物成分。PRR启动细胞内信号，其产生具有刺激T细胞应答的能力的DC。Dectin-1是一种识别β-葡聚糖的PRR，β-葡聚糖是许多真菌外细胞壁的主要成分。在这里，我们表明Dectin-1通过磷脂酶（PLC）γ2信号转导激活DC。PLCγ2缺陷型DC不能扩增抗原特异性T细胞并诱导响应于β葡聚糖的TH 1和TH 17分化。从机制上讲，PLCγ2-缺乏会损害DC在暴露于β-葡聚糖后分泌极化细胞因子的能力。Dectin-1需要PLCγ2激活MAPK、AP-1和NF-κB，从而诱导细胞因子基因表达。此外，PLCγ2控制Dectin-1-介导的NFAT激活和NFAT依赖性基因（如IL-2、环氧化酶-2和Egr转录因子）的诱导。我们得出结论，PLCγ2是一种重要的信号传导介质，可以改变DC基因表达程序，激活DC对含β-葡聚糖病原体的反应。
DC recognize microbial components through an array of receptors known as PRR. PRR initiate intracellular signals, which engender DC with the capacity to stimulate T‐cell responses. Dectin‐1 is a PRR that recognizes β‐glucan, a major constituent of many fungi's outer cell wall. Here we show that Dectin‐1 activates DC through phospholipase (PLC)γ2 signaling. PLCγ2‐deficient DC were unable to expand antigen‐specific T cells and induce TH1 and TH17 differentiation in response to β‐glucan. Mechanistically, PLCγ2‐deficiency impaired the capacity of DC to secrete polarizing cytokines following exposure to β‐glucan. Dectin‐1 required PLCγ2 to activate MAPK, AP‐1 and NF‐κB, which induce cytokine gene expression. Moreover, PLCγ2 controlled Dectin‐1‐mediated NFAT activation and induction of NFAT‐dependent genes such as IL‐2, cyclooxigenase‐2 and Egr transcription factors. We conclude that PLCγ2 is a crucial signaling mediator that modifies DC gene expression program to activate DC responses to β‐glucan‐containing pathogens.
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影响因子：
15.9
作者：
Dillon, S;Agrawal, S;Pulendran, B
通讯作者：
Pulendran, B
影响因子：
20.3
作者：
Guha, M;O'Connell, MA;Mackman, N
通讯作者：
Mackman, N
影响因子：
2.2
作者：
Bender, A;Sapp, M;Bhardwaj, N
通讯作者：
Bhardwaj, N
影响因子：
32.4
作者：
Wang, DM;Feng, J;Ihle, JN
通讯作者：
Ihle, JN