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人工磷脂酰丝氨酸脂质体在体外可模拟凋亡细胞,抑制小鼠骨髓来源树突状细胞对1-氯-2,4-二硝基苯的成熟及免疫刺激功能。

Artificial phosphatidylserine liposome mimics apoptotic cells in inhibiting maturation and immunostimulatory function of murine myeloid dendritic cells in response to 1-chloro-2,4-dinitrobenze in vitro.

作者信息

Shi Dongmei, Fu Meng, Fan Pinshen, Li Wei, Chen Xinhui, Li Chenxin, Qi Xianlong, Gao Tianwen, Liu Yufeng

机构信息

Dermatology Center of Chinese PLA, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.

出版信息

Arch Dermatol Res. 2007 Sep;299(7):327-36. doi: 10.1007/s00403-007-0770-9. Epub 2007 Jul 21.

Abstract

Phosphatidylserine (PS) exposed on the apoptotic cell surface inhibits inflammatory responses, implying that PS may regulate the function of dendritic cells (DCs) after being phagocytosed by the latter. Here we use PS liposomes to investigate the effects of PS on the maturation and immunostimulatory functions of DCs in response to the challenge of 1-chloro-2,4-dinitrobenze (DNCB) in vitro. We demonstrate that after treatment with PS, murine DCs display reduced expression of MHC II, CD80, CD86 and CD40, but increased programmed death ligand-1 (PD-L1 and PD-L2); and increased IL-10 and inhibited IL-12 cytokine production. PS-treated DCs exhibit normal endocytic function, but ability to stimulate allogeneic T cells is reduced, similar to immature dendritic cell (iDCs). Treatment of DCs with PS liposomes also suppressed DNCB induced CD4 + T cell proliferation and IFN-gamma production. Addition of exogenous IL-12p70 during the DC-T cell co-culture restored their IFN-gamma production. Furthermore, PS-treated DCs enhance the ratio of CD4(+) CD25(high)Foxp3(+) T cells to CD4(+) T cells and PD-1 expression on CD4(+) T cells. These data demonstrate that PS liposomes have therapeutic potential in allergic contact dermatitis (ACD).

摘要

暴露于凋亡细胞表面的磷脂酰丝氨酸(PS)可抑制炎症反应,这意味着PS在被树突状细胞(DC)吞噬后可能调节其功能。在此,我们使用PS脂质体在体外研究PS对DC在1-氯-2,4-二硝基苯(DNCB)刺激下的成熟和免疫刺激功能的影响。我们证明,用PS处理后,小鼠DC的MHC II、CD80、CD86和CD40表达降低,但程序性死亡配体-1(PD-L1和PD-L2)表达增加;IL-10增加,IL-12细胞因子产生受到抑制。经PS处理的DC表现出正常的内吞功能,但刺激同种异体T细胞的能力降低,类似于未成熟树突状细胞(iDC)。用PS脂质体处理DC也抑制了DNCB诱导的CD4 + T细胞增殖和IFN-γ产生。在DC-T细胞共培养期间添加外源性IL-12p70可恢复其IFN-γ产生。此外,经PS处理的DC提高了CD4(+) CD25(high)Foxp3(+) T细胞与CD4(+) T细胞的比例以及CD4(+) T细胞上PD-1的表达。这些数据表明PS脂质体在过敏性接触性皮炎(ACD)中具有治疗潜力。

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