Functional maturation of lamina propria dendritic cells by activation of NKT cells mediates the abrogation of oral tolerance
Functional maturation of lamina propria dendritic cells by activation of NKT cells mediates the abrogation of oral tolerance
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DOI：
10.1002/eji.200838159
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发表时间：
2008-10-01
影响因子：
5.4
通讯作者：
Kang, Chang-Yuil
中科院分区：
文献类型：
--
作者：
Chang, Jae-Hoon;Lee, Jung-Mi;Kang, Chang-Yuil
我们先前的研究表明，尽管全身应用α-半乳糖基神经酰胺(α-GalCer)或激动型抗CD40抗体可诱导肠系膜淋巴结树突状细胞(DC)功能成熟，但只有前者成功地打破了口服耐受的诱导。在这项研究中，我们寻找导致口服耐受性中断的主要因素。我们发现固有层(LP)-DC负责口腔OVA的呈现，而Peyer‘s补片不是诱导口服耐受所必需的。因此，我们研究了LP-DC的作用。用aGalCer处理而不用抗CD40处理可在早期诱导LP-DC的充分成熟。Lp-DC的这种功能激活是由大量存在于小肠固有层(SI-LP)的NKT细胞的强烈激活所介导的，而干扰素-γ部分参与了Lp-DC的激活。从经α-GalCer处理的卵清蛋白喂养的小鼠分离的LP-DC可诱导原始的CD4(+)T细胞分化为Th1和Th2，并与Foxp3(+)数量的减少有关。相反，从经抗CD40处理的卵清蛋白喂养的小鼠分离的LP-DC不能诱导Th细胞分化，但能诱导更多的Foxp3(+)CD4(+)T细胞。我们的结果表明，在SI-LP中NKT细胞的触发下，SI-LP中捕获抗原的DC的功能成熟是消除口服耐受诱导所必需的。
We previously showed that although systemic administration of a-galactosylceramide (alpha GalCer) or agonistic anti-CD40 induced functional maturation of dendritic cells (DC) in mesenteric lymph nodes, only the former treatment succeeded in breaking the induction of oral tolerance. in this study, we looked for the essential factor responsible for the disruption of oral tolerance. We found that lamina propria (LP)-DC was responsible for the oral OVA presentation and that Peyer's patch was not essential for the induction of oral tolerance. Therefore, we investigated the role of LP-DC. Treatment with aGalCer but not with anti-CD40 induced the full maturation of LP-DC at an early time point. This functional activation of LP-DC was mediated by strong activation of NKT cells that reside abundantly in the small intestinal lamina propria (SI-LP) and interferon-gamma partially contributed to the LP-DC activation. LP-DC isolated from alpha GalCer-treated OVA-fed mice induced the differentiation of naive CD4(+) T cells into Th1 and Th2 and was associated with the reduced Foxp3(+) population. In contrast, LP-DC isolated from anti-CD40-treated OVA-fed mice failed to generate Th cell differentiation but induced more Foxp3(+) CD4(+) T cells. Our results demonstrate that triggered by NKT cells in SI-LP, functional maturation of Ag-capturing DC from SI-LP is necessary for the abrogation of oral tolerance induction.