Regulatory role of DC-derived osteopontin in systemic allergen sensitization
Regulatory role of DC-derived osteopontin in systemic allergen sensitization
复制标题
DOI：
10.1002/eji.200838970
复制
发表时间：
2009-12-01
影响因子：
5.4
通讯作者：
Huang, Shau-Ku
中科院分区：
文献类型：
--
作者：
Kurokawa, Masatsugu;Konno, Satoshi;Huang, Shau-Ku
骨桥蛋白（OPN）是一种具有广泛功能的分泌型磷酸糖蛋白，参与多种病理生理过程。然而，OPN在IgE和Th 2相关过敏反应中的作用仍不完全明确。本研究的目的是阐明OPN在小鼠全身过敏原致敏中的作用。当与OPN+/+小鼠相比时，在OPN-/-小鼠中发现OVA诱导的IgE水平显著增加。OPN-/- DC表现出增强来自致敏OPN+/+小鼠的CD 4（+）T细胞中Th 2细胞因子产生的能力增加。此外，与WT DC相比，在LPS刺激的OPN-/- DC中观察到IL-12 p70表达水平显著降低，并且通过添加重组OPN（rOPN），该降低是可逆的。rOPN能够抑制OVA诱导的CD 4和OPN-/- DC培养物中IL-13的产生，但这种抑制活性被添加抗IL-12 Ab所中和。此外，rOPN体内给药抑制了OVA特异性IgE的产生;然而，这种抑制作用在IL-12缺陷小鼠中被消除。这些结果表明，DC衍生的OPN在系统性过敏原致敏的发展中起调节作用，其至少部分地通过内源性IL-12的产生介导。
Osteopontin (OPN) is a secreted phosphoglycoprotein with a wide range of functions, and is involved in various pathophysiological conditions. However, the role of OPN in IgE and Th2-associated allergic responses remains incompletely defined. The aim of this study was to elucidate the role of OPN in systemic allergen sensitization in mice. When compared with OPN+/+ mice, significantly increased levels of OVA-induced IgE were found in OPN-/- mice. OPN-/- DC demonstrated an increased capacity to enhance Th2 cytokine production in CD4(+) T cells from sensitized OPN+/+ mice. Furthermore, significantly reduced levels of IL-12p70 expression were seen in LPS-stimulated OPN-/- DC as compared with the WT DC, and the reduction was reversible by the addition of recombinant OPN (rOPN). rOPN was able to suppress OVA-induced IL-13 production in the cultures of CD4 and OPN-/- DC, but this inhibitory activity was neutralized by the addition of anti-IL-12 Ab. In addition, administration of rOPN in vivo suppressed OVA-specific IgE production; however, this suppressive effect was abrogated in IL-12-deficient mice. These results indicate that DC-derived OPN plays a regulatory role in the development of systemic allergen sensitization, which is mediated, at least in part, through the production of endogenous IL-12.