IL-10 Enhances IgE-Mediated Mast Cell Responses and Is Essential for the Development of Experimental Food Allergy in IL-10-Deficient Mice.
IL-10 Enhances IgE-Mediated Mast Cell Responses and Is Essential for the Development of Experimental Food Allergy in IL-10-Deficient Mice.
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IL-10能增强IgE介导的肥大细胞反应，对IL-10缺陷小鼠实验性食物过敏的发生至关重要
DOI：
10.4049/jimmunol.1600066
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发表时间：
2016-06-15
期刊：
影响因子：
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通讯作者：
Mathias CB
中科院分区：
文献类型：
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作者：
Polukort SH;Rovatti J;Carlson L;Thompson C;Ser-Dolansky J;Kinney SR;Schneider SS;Mathias CB
IL-10是一种关键的多效性细胞因子，可以促进和抑制Th 2依赖性过敏反应。在此，我们证明了IL-10在促进肥大细胞扩增和IgE介导的食物过敏的发展中的新作用。致敏BALB/c小鼠口服卵清蛋白激发导致肠道肥大细胞反应增强，伴有过敏性腹泻、肥大细胞活化和Th 2细胞因子占优势，包括IL-10表达增强。相比之下，与WT对照组相比，IL-10−/−小鼠肠道过敏反应（包括腹泻、肥大细胞活化和Th 2细胞因子产生）的发生显著减弱。IL-10还直接促进肥大细胞的扩增、存活和活化，增加肥大细胞上的Fc ε RI表达，并增强肥大细胞细胞因子的产生。IL-10−/−肥大细胞的功能能力降低，可通过外源性IL-10恢复。同样，IL-10−/−小鼠中减弱的被动过敏反应可以通过IL-10给药恢复。WT肥大细胞的过继转移恢复了IL-10−/−小鼠的过敏症状，表明在这些动物中观察到的减毒表型是由于IL-10应答性肥大细胞缺乏所致。最后，WT CD 4 T细胞的转移也恢复了IL-10−/−小鼠的过敏性腹泻和肠道肥大细胞数量，表明IL-10介导的肠道肥大细胞扩增的调节是T细胞依赖性的。我们的观察结果表明，IL-10在驱动粘膜肥大细胞扩增和活化中起着关键作用，这表明在其缺失的情况下，肥大细胞功能受损，导致食物过敏症状减弱。
IL-10 is a key pleiotropic cytokine that can both promote and curb Th2-dependent allergic responses. Herein we demonstrate a novel role for IL-10 in promoting mast cell expansion and the development of IgE-mediated food allergy. Oral ovalbumin challenge in sensitized BALB/c mice resulted in a robust intestinal mast cell response accompanied by allergic diarrhea, mast cell activation, and a predominance of Th2 cytokines, including enhanced IL-10 expression. In contrast, the development of intestinal anaphylaxis including diarrhea, mast cell activation, and Th2 cytokine production was significantly attenuated in IL-10−/− mice compared to WT controls. IL-10 also directly promoted the expansion, survival, and activation of mast cells, increased FcɛRI expression on mast cells, and enhanced the production of mast cell cytokines. IL-10−/− mast cells had reduced functional capacity, which could be restored by exogenous IL-10. Similarly, attenuated passive anaphylaxis in IL-10−/− mice could be restored by IL-10 administration. The adoptive transfer of WT mast cells restored allergic symptoms in IL-10−/− mice, suggesting that the attenuated phenotype observed in these animals is due to a deficiency in IL-10-responding mast cells. Lastly, transfer of WT CD4 T cells also restored allergic diarrhea and intestinal mast cell numbers in IL-10−/− mice, suggesting that the regulation of IL-10-mediated intestinal mast cell expansion is T cell-dependent. Our observations demonstrate a critical role for IL-10 in driving mucosal mast cell expansion and activation, suggesting that in its absence, mast cell function is impaired, leading to attenuated food allergy symptoms.