Shiokawa Aya, Tanabe Kosuke, Tsuji Noriko M, Sato Ryuichiro, Hachimura Satoshi
Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
Immunol Lett. 2009 Jun 30;125(1):7-14. doi: 10.1016/j.imlet.2009.05.002. Epub 2009 May 14.
Oral tolerance is a key feature of intestinal immunity, generating systemic tolerance to ingested antigens (Ag). Dendritic cells (DC) have been revealed as important immune regulators, however, the precise role of DC in oral tolerance induction remains unclear. We investigated the characteristics of DC in spleen, mesenteric lymph node (MLN), and Peyer's patch (PP) after oral Ag administration in a TCR-transgenic mouse model. DC from PP and MLN of tolerized mice induced IL-10 production but not Foxp3 expression in cocultured T cells. IL-10 production was markedly increased after 5-7-day Ag administration especially in PP DC. On the other hand, IL-27 production was increased after 2-5-day Ag administration. CD11b(+) DC, which increased after ingestion of Ag, prominently expressed IL-10 and IL-27 compared with CD11b(-) DC. These results suggest that IL-10 and IL-27 producing DC are increased by interaction with antigen specific T cells in PP, and these DC act as an inducer of IL-10 producing T cells in oral tolerance.
口服耐受是肠道免疫的一个关键特征，可对摄入的抗原（Ag）产生全身耐受性。树突状细胞（DC）已被揭示为重要的免疫调节因子，然而，DC在口服耐受诱导中的精确作用仍不清楚。我们在TCR转基因小鼠模型中研究了口服Ag后脾脏、肠系膜淋巴结（MLN）和派尔集合淋巴结（PP）中DC的特征。来自耐受小鼠的PP和MLN中的DC在共培养的T细胞中诱导IL-10的产生，但不诱导Foxp3的表达。在给予Ag 5-7天后，IL-10的产生显著增加，尤其是在PP DC中。另一方面，在给予Ag 2-5天后，IL-27的产生增加。与CD11b（-）DC相比，摄入Ag后增加的CD11b（+）DC显著表达IL-10和IL-27。这些结果表明，产生IL-10和IL-27的DC通过与PP中抗原特异性T细胞相互作用而增加，并且这些DC在口服耐受中作为产生IL-10的T细胞的诱导剂发挥作用。
