Phosphatidylserine regulates the maturation of human dendritic cells
Phosphatidylserine regulates the maturation of human dendritic cells
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DOI：
10.4049/jimmunol.173.5.2985
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发表时间：
2004-09-01
影响因子：
4.4
通讯作者：
Shilyansky, J
中科院分区：
文献类型：
--
作者：
Chen, X;Doffek, K;Shilyansky, J
磷脂酰丝氨酸（PS），这是暴露在凋亡细胞的表面，已牵连在免疫调节。然而，PS对树突状细胞（DC）的成熟和功能的影响，在免疫激活和调节中起着核心作用，尚未被描述。含有PS或磷脂酰胆碱的大单层脂质体分别用于模拟凋亡细胞和活细胞的质膜磷脂组合物。PS脂质体抑制人DC对LPS的反应中HLA-ABC、HLA-DR、CD 80、CD 86、CD 40和CD 83的上调以及IL-12 p70的产生。PS不直接影响DC的存活率，但使DC在LPS作用下易发生凋亡。暴露于PS的DC刺激同种异体T细胞增殖和激活产生IFN-γ的CD 4（+）T细胞的能力降低。外源性IL-12可恢复CD 4（+）T细胞产生IFN-γ。此外，活化的CTL增殖不良，以同源抗原提出的DC暴露于PS。我们的研究结果表明，PS暴露提供了足够的信号，以抑制DC成熟和调节适应性免疫反应。
Phosphatidylserine (PS), which is exposed on the surface of apoptotic cells, has been implicated in immune regulation. However, the effects of PS on the maturation and function of dendritic cells (DCs), which play a central role in both immune activation and regulation, have not been described. Large unilamellar liposomes containing PS or phosphatidylcholine were used to model the plasma membrane phospholipid composition of apoptotic and live cells, respectively. PS liposomes inhibited the up-regulation of HLA-ABC, HLA-DR, CD80, CD86, CD40, and CD83, as well as the production of IL-12p70 by human DCs in response to LPS. PS did not affect DC viability directly but predisposed DCs to apoptosis in response to LPS. DCs exposed to PS had diminished capacity to stimulate allogeneic T cell proliferation and to activate IFN-gamma-producing CD4(+) T cells. Exogenous IL-12 restored IFN-gamma production by CD4(+) T cells. Furthermore, activated CTLs proliferated poorly to cognate Ag presented by DCs exposed to PS. Our findings suggest that PS exposure provides a sufficient signal to inhibit DC maturation and to modulate adaptive immune responses.