Alcohol facilitates CD1d loading, subsequent activation of NKT cells, and reduces the incidence of diabetes in NOD mice.
Alcohol facilitates CD1d loading, subsequent activation of NKT cells, and reduces the incidence of diabetes in NOD mice.
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DOI：
10.1371/journal.pone.0017931
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发表时间：
2011-04-01
期刊：
影响因子：
3.7
通讯作者：
Nieuwenhuis EE
中科院分区：
文献类型：
--
作者：
Buschard K;Hansen AK;Jensen K;Lindenbergh-Kortleve DJ;de Ruiter LF;Krohn TC;Hufeldt MR;Vogensen FK;Aasted B;Osterbye T;Roep BO;de Haar C;Nieuwenhuis EE
乙醇(酒精)是一种部分疏水的洗涤剂，可能会影响糖脂的可及性，从而影响这些分子的免疫效果。这项研究包括使用α-半乳糖神经酰胺(αGalCer)的体外细胞测试，以及体内NOD小鼠实验，检测糖尿病发病率并进行行为和细菌分析。浓度从0.6%到2.5%的酒精可使αGalCer刺激的NKT细胞产生IL-2增加60%(p<；0.05)。随着酒精浓度的增加，α-GalCer在HeLa细胞上的表达显著增加，提示酒精促进了α-GalCer对CD1d的被动负载。NOD小鼠被发现在他们的饮用水中耐受5%的乙醇，没有肝功能受损的迹象。有了这种治疗，糖尿病的发病率显著下降。酒精处理组小鼠脾、肝CD3+CD49b+NKT细胞数明显高于对照组(P<0.05)，而CD4+Foxp3+调节性T细胞数无明显差异。在酒精处理的小鼠24小时血液样本中检测到干扰素-γ浓度升高。行为学研究表明，饮酒小鼠的态度没有改变，盲肠样本的细菌组成也没有受到酒精的影响，这使它们失去了作为保护机制的资格。酒精促进糖脂的摄取和刺激NKT细胞，这是已知的抵消1型糖尿病发展的因素。我们认为这是酒精治疗降低NOD小鼠糖尿病发病率的作用机制。这一点得到了流行病学的证实，表明酒精对减轻动脉粥样硬化和相关疾病的严重程度有好处。
Ethanol (‘alcohol’) is a partly hydrophobic detergent that may affect the accessibility of glycolipids thereby influencing immunological effects of these molecules. The study included cellular in vitro tests using α-galactosylceramide (αGalCer), and in vivo NOD mice experiments detecting diabetes incidence and performing behavioural and bacterial analyses. Alcohol in concentrations from 0.6% to 2.5% increased IL-2 production from NKT cells stimulated with αGalCer by 60% (p<0.05). CD1d expressed on HeLa cells contained significantly increasing amounts of αGalCer with increasing concentrations of alcohol, suggesting that alcohol facilitated the passive loading of αGalCer to CD1d. NOD mice were found to tolerate 5% ethanol in their drinking water without signs of impairment in liver function. Giving this treatment, the diabetes incidence declined significantly. Higher numbers of CD3+CD49b+ NKT cells were found in spleen and liver of the alcohol treated compared to the control mice (p<0.05), whereas the amount of CD4+Foxp3+ regulator T cells did not differ. Increased concentrations of IFN-γ were detected in 24-hour blood samples of alcohol treated mice. Behavioural studies showed no change in attitude of the ethanol-consuming mice, and bacterial composition of caecum samples was not affected by alcohol, disqualifying these as protective mechanisms. Alcohol facilitates the uptake of glycolipids and the stimulation of NKT cells, which are known to counteract Type 1 diabetes development. We propose that this is the acting mechanism by which treatment with alcohol reduces the incidence of diabetes in NOD mice. This is corroborated by epidemiology showing beneficial effect of alcohol to reduce the severity of atherosclerosis and related diseases.
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影响因子：
15.9
作者：
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通讯作者：
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影响因子：
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DOI：
10.1073/pnas.121169698
发表时间：
2001-06-05
影响因子：
11.1
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Sarvetnick, N