Periportal and sinusoidal liver dendritic cells suppressing T helper type 1-mediated hepatitis

Periportal and sinusoidal liver dendritic cells suppressing T helper type 1-mediated hepatitis
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门静脉周围和肝窦树突状细胞抑制辅助性T细胞1型介导的肝炎

DOI:
10.1136/gut.2007.121251
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发表时间:
2007
期刊:
Gut
影响因子:
24.5
通讯作者:
Y. Wakatsuki
Y. Wakatsuki
中科院分区:
医学1区
文献类型:
--
作者:
Tomohiro Watanabe;Hiroaki Katsukura;T. Chiba;T. Kita;Y. Wakatsuki

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背景:最近,我们发现门静脉耐受与肝脏Th2细胞的产生和Th1细胞的凋亡有关,而肝门周围和肝窦内的抗原提呈树突状细胞(DC)调节Th2细胞的产生和Th1细胞的凋亡。目的:检测体内负载抗原的门静脉周围树突状细胞和肝窦内树突状细胞能否抑制全身注射抗原激活的Th1细胞所致的肝损伤。方法:将卵白蛋白(OVA)特异性的CD4+T细胞过继转移到BALB/c小鼠体内,静脉注射含OVA的脂质体,建立银屑病特异性肝炎模型。从饲喂卵清蛋白的小鼠肝脏中获得CD11c+细胞,然后将其移植到这些小鼠体内。结果:OVA组小鼠肝脏CD11c+细胞的转移可完全抑制肝损伤,其机制可能与OVA特异性的CD4+T细胞的凋亡和Th2细胞的出现有关。CD11c+细胞的转移和OVA皮下注射可增强受体小鼠的OVA特异性IgE抗体和Th2细胞因子应答。结论:门静脉负载抗原的门静脉周围和肝窦DC可诱导肝脏Th2应答,预防Th1细胞所致的肝损伤。
Background: Recently, we found that portal vein tolerance is associated with generation of Th2 cells and apoptosis of Th1 cells in the liver, which is regulated by antigen (Ag)-presenting dendritic cells (DCs) in the periportal area and sinusoids. Aim: In this study, we tested whether the periportal and sinusoidal DCs, which were loaded with an Ag in vivo, can inhibit liver injury caused by Th1 cells activated by the Ag administered systemically. Methods: Ag-specific hepatitis model was created by adoptively transferring ovalbumin (OVA)-specific CD4+ T cells to BALB/c mice and venous injection of OVA-containing liposomes. Liver CD11c+ cells obtained from mice fed OVA were then transferred into these mice. Results: The transfer of liver CD11c+ cells from OVA-fed mice completely inhibited hepatic injury, which was associated with apoptosis of OVA-specific CD4+ T cells and emergence of Th2 cells in the liver. Transfer of CD11c+ cells and subcutaneous OVA challenge led to enhancement of OVA-specific IgE Ab as well as Th2 cytokine responses in the recipient mice. Conclusions: Periportal and sinusoidal DCs loaded with an Ag in the portal vein can induce Th2 response in the liver and prevent hepatic injury caused by Th1 cells.
DOI: 10.1016/j.immuni.2006.06.018
发表时间: 2006-09-01
期刊: IMMUNITY
影响因子: 32.4
作者:
Watanabe, Tomohiro;Kitani, Atsushi;Strober, Warren
通讯作者: Strober, Warren
树突状细胞是肝移植耐受的关键吗?
DOI: 10.1016/s0167-5699(98)01378-4
发表时间: 1999
期刊: Immunology today
影响因子: --
作者:
Thomson,AW;Lu,L
通讯作者: Lu,L