The Liver Mediates Apoptotic Cell‐Induced Immune Regulation
The Liver Mediates Apoptotic Cell‐Induced Immune Regulation
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肝脏介导凋亡细胞诱导的免疫调节
DOI：
10.1111/j.1365-3083.2008.02141.x
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发表时间：
2008
影响因子：
3.7
通讯作者：
Z. Chen
中科院分区：
文献类型：
--
作者：
Y. Wang;Y. Gao;X. Yuan;W. Xia;Y. Luo;E. Sun;Z. Chen
已证实同种异体凋亡细胞可诱导同种异体移植耐受，但其机制尚不清楚。本研究调查了可能发生致耐受性免疫应答的器官。通过荧光显微镜和流式细胞术研究受体器官中活的或凋亡的CFSE+脾细胞的分布以及肝脏抗原呈递细胞（APC）的吞噬作用，并通过多重和ELISA分析细胞因子表达。结果发现，同种异体或自体凋亡细胞优先积累在肝脏内的30分钟内，在60分钟达到高峰，并在12小时后消失，而这些细胞几乎没有出现在脾脏。 肝脏中的蓄积具有凋亡细胞特异性，因为同种异体和自体活脾细胞均完全沉积在脾脏中。肝巨噬细胞包括枯否细胞、肝窦内皮细胞和树突状细胞，在体内外均能有效吞噬凋亡细胞。虽然在同种异体凋亡细胞的接受者的脾脏和肝脏中发现了Th1细胞因子谱，但在肝脏中特异性地启动了快速且一致的Th2细胞因子谱。由此可见，肝脏APC吞噬供者凋亡细胞并诱导肝脏特异性Th2细胞因子，这可能有助于供者凋亡细胞诱导同种异体移植耐受的机制。
Allogeneic apoptotic cells have been demonstrated to induce allograft tolerance, but the mechanisms for this remain unclear. The study presented here investigates organs in which the tolerogenic immune responses may occur. Distribution of live or apoptotic CFSE+ splenocytes in recipients’ organs and phagocytosis by liver antigen‐presenting cells (APC) were investigated by fluorescence microscopy and flow cytometry, and cytokine expression was analysed by Multiplex and ELISA. It was found that allogeneic or autogenic apoptotic cells preferentially accumulated in the liver within 30 min, peaked at 60 min, and disappeared at 12 h after infusion, whereas these cells scarcely appeared in the spleen. The accumulation in the liver was apoptotic cell‐specific as both allogeneic and autogenic live splenocytes were completely deposited in the spleen. Liver phagocytes, including Kupffer cells, liver sinusoidal endothelial cells and dendritic cells, all efficiently phagocytized apoptotic cells in vitro and in vivo. Although a Th1 cytokine profile found both in the spleen and liver in the recipients of allogeneic apoptotic cells, a rapid and consistent Th2 cytokine profile specifically was initiated in the liver. From this, we conclude that liver APC phagocytize donor apoptotic cells and induce liver‐specific Th2 cytokines, which may contribute to the mechanisms of allograft tolerance induced by donor apoptotic cells.
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影响因子：
15.9
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
影响因子：
20.3
作者：
Morelli, AE;Larregina, AT;Thomson, AW
通讯作者：
Thomson, AW
影响因子：
32.4
作者：
HUANG, L;SOLDEVILA, G;CRISPE, IN
通讯作者：
CRISPE, IN
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