Induction of Interleukin-9-Producing Mucosal Mast Cells Promotes Susceptibility to IgE-Mediated Experimental Food Allergy.
Induction of Interleukin-9-Producing Mucosal Mast Cells Promotes Susceptibility to IgE-Mediated Experimental Food Allergy.
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DOI：
10.1016/j.immuni.2015.08.020
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发表时间：
2015-10-20
期刊：
影响因子：
32.4
通讯作者：
Wang YH
中科院分区：
文献类型：
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作者：
Chen CY;Lee JB;Liu B;Ohta S;Wang PY;Kartashov AV;Mugge L;Abonia JP;Barski A;Izuhara K;Rothenberg ME;Finkelman FD;Hogan SP;Wang YH
实验性ige介导的食物过敏依赖于由白细胞介素-9驱动的肠道过敏反应。然而，IL-9的主要细胞来源和食物致肠道过敏反应易感性的机制尚不清楚。在此，我们报道了鉴定出多功能产生IL-9的粘膜肥大细胞（MMC9s），它们分别可以分泌大量的IL-9和IL-13来响应IL-33，以及分泌大量的肥大细胞蛋白酶-1 （MCPt-1）来响应抗原和IgE复合物交联。重复的胃内抗原刺激诱导MMC9发育，这需要T细胞、IL-4和STAT6转录因子，但不需要IL-9信号。切除MMC9诱导的小鼠没有发生肠道肥大细胞增多症，这导致食物过敏症状减轻，可以通过过继转移MMC9来恢复。最后，发生食物过敏的特应性患者表现出肠道il - 9和mc特异性转录物的表达增加。因此，诱导mmc9是获得对ige介导的食物过敏易感性的关键步骤。
Experimental IgE-mediated food allergy depends on intestinal anaphylaxis driven by interleukin (IL)-9. However, the primary cellular source of IL-9 and the mechanisms underlying the susceptibility to food-induced intestinal anaphylaxis remain unclear. Herein, we have reported the identification of multifunctional IL-9-producing mucosal mast cells (MMC9s) that can secrete prodigious amounts of IL-9 and IL-13 in response to IL-33, and mast cell protease-1 (MCPt-1) in response to antigen and IgE complex crosslinking, respectively. Repeated intragastric antigen challenge induced MMC9 development that required T cells, IL-4, and STAT6 transcription factor, but not IL-9 signals. Mice ablated of MMC9 induction failed to develop intestinal mastocytosis, which resulted in decreased food allergy symptoms that could be restored by adoptively transferred MMC9s. Finally, atopic patients that developed food allergy displayed increased intestinal expression of Il9 and MC-specific transcripts. Thus, the induction of MMC9s is a pivotal step to acquire the susceptibility to IgE-mediated food allergy.