Critical role for syndecan-4 in dendritic cell migration during development of allergic airway inflammation
Critical role for syndecan-4 in dendritic cell migration during development of allergic airway inflammation
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DOI：
10.1038/ncomms8554
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发表时间：
2015-07-01
影响因子：
16.6
通讯作者：
Averbeck, Marco
中科院分区：
文献类型：
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作者：
Polte, Tobias;Petzold, Susanne;Averbeck, Marco
多配体蛋白聚糖4（Syndecan-4，SDC 4）表达于树突状细胞（dendritic cells，DC）和活化的T细胞上，在DC运动中起关键作用，并已被证明是活化的T细胞驱动的疾病的潜在靶点。在本研究中，我们探讨了SDC 4在T辅助细胞2介导的过敏性哮喘的发展中的作用。使用SDC 4缺陷小鼠或抗SDC 4抗体，我们表明，SDC 4信号的缺乏或阻断卵清蛋白致敏小鼠的结果在减少哮喘表型与对照动物相比。最重要的是，使用抗SDC 4抗体，即使是已建立的哮喘也显著降低。SDC 4信号传导紊乱导致抗原呈递DC的运动性和定向迁移受损，因此导致修饰的致敏作用，从而减少气道炎症。我们的研究结果表明，SDC 4在哮喘诱导中起着重要作用，并表明SDC 4作为这种疾病的治疗干预的可能靶点。
Syndecan-4 (SDC4), expressed on dendritic cells (DCs) and activated T cells, plays a crucial role in DC motility and has been shown as a potential target for activated T-cell-driven diseases. In the present study, we investigate the role of SDC4 in the development of T-helper 2 cell-mediated allergic asthma. Using SDC4-deficient mice or an anti-SDC4 antibody we show that the absence or blocking of SDC4 signalling in ovalbumin-sensitized mice results in a reduced asthma phenotype compared with control animals. Most importantly, even established asthma is significantly decreased using the anti-SDC4 antibody. The disturbed SDC4 signalling leads to an impaired motility and directional migration of antigen-presenting DCs and therefore, to a modified sensitization leading to diminished airway inflammation. Our results demonstrate that SDC4 plays an important role in asthma induction and indicate SDC4 as possible target for therapeutic intervention in this disease.