Inhibition of T helper 2-type responses, IgE production and eosinophilia by synthetic lipopeptides
Inhibition of T helper 2-type responses, IgE production and eosinophilia by synthetic lipopeptides
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DOI：
10.1002/eji.200323329
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发表时间：
2003-10-01
影响因子：
5.4
通讯作者：
Alkan, SS
中科院分区：
文献类型：
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作者：
Akdis, CA;Kussebi, F;Alkan, SS
在过敏和哮喘中，T辅助细胞(Th)1、Th2和T调节细胞因子反应之间的精细平衡似乎向Th2转移。在这里，我们报告了含有革兰氏阴性细菌脂蛋白典型脂部分的合成脂肽刺激独特的调节细胞因子模式并抑制几种与Th2细胞相关的现象。合成脂肽的最有效类似物，脂肽CGP40(LP40)在MyD88基因缺陷的小鼠中不起作用，并刺激TLR2，而不是TLR4。LP40可促进人T细胞产生干扰素-γ和IL-10，但不能产生IL-4和IL-5。此外，脂肽对TLR-2的激活促进了初始T细胞向产生IL-10和干扰素-γ的T细胞的体外分化，并抑制了Th2细胞产生IL-4。因此，LP40可抑制过敏原、抗IGD抗体、巴西拟青虫或小鼠获得性免疫缺陷病毒诱导的IgE生成。此外，LP40还能消除卵清蛋白诱导的小鼠肺嗜酸性炎症，抑制曼氏血吸虫卵诱导的小鼠肉芽肿大小和嗜酸性粒细胞计数。这些结果表明，脂肽对TLR-2的刺激是一种可能通过调节细胞因子失衡来治疗过敏和哮喘的新途径。
In allergy and asthma, the fine balance between the T helper (Th) 1, Th2 and T regulatory cytokine responses appears to be shifted towards Th2. Here, we report that synthetic lipopeptides which contain the typical lipid part of the lipoprotein of gram-negative bacteria stimulate a distinct regulatory cytokine pattern and inhibit several Th2 cell-related phenomena. The most potent analogue of synthetic lipopeptides, lipopeptide CGP 40774 (LP40) was not active in MyD88-deficient mice and stimulated Toll-like receptor (TLR)-2, but not TLR-4. LP40 potentiated the production of IFN-gamma and IL-10, but not IL-4 and IL-5 by human T cells. In addition, triggering of TLR-2 by lipopeptides promoted the in vitro differentiation of naive T cells towards IL-10- and IFN-gamma-producing T cells and suppressed IL-4 production by Th2 cells. Accordingly, LP40 inhibited IgE production induced by allergen, anti-IgD antibody, Nippostrongylus brasiliensis or murine acquired immunodeficiency virus. Furthermore, ovalbumin-induced lung eosinophilic inflammation was abolished and Schistosoma mansoni egg-induced granuloma size and eosinophil counts were suppressed in mice by LP40. These results demonstrate that stimulation of TLR-2 by lipopeptides represents a novel way for possible treatment of allergy and asthma by regulating the disrupted cytokine balance.