The Allergen Der p3 from House Dust Mite Stimulates Store-Operated Ca2+ Channels and Mast Cell Migration through PAR4 Receptors.
The Allergen Der p3 from House Dust Mite Stimulates Store-Operated Ca2+ Channels and Mast Cell Migration through PAR4 Receptors.
复制标题
DOI：
10.1016/j.molcel.2018.03.025
复制
发表时间：
2018-04
期刊：
影响因子：
16
通讯作者：
Yu-ping Lin;C. Nelson;H. Kramer;A. Parekh
中科院分区：
文献类型：
--
作者：
Yu-ping Lin;C. Nelson;H. Kramer;A. Parekh
室内尘螨是人体常年性空气过敏原的主要来源。这些过敏原如何激活先天免疫和适应性免疫尚不清楚，因此，没有针对螨虫过敏原的治疗方法。在这里，我们表明尘螨提取物激活储存操作的Ca2+通道，这是肺中许多细胞类型中的常见信号模块。螨提取物激活通道孔隙形成的Orai1亚基需要STIM1蛋白的门控。虽然螨虫提取物刺激蛋白酶激活受体2型（PAR2）和PAR4受体，Ca2+内流更紧密地耦合到PAR4途径。我们确定了丝氨酸蛋白酶过敏原Der p3在刺激Orai1通道中的主要作用，并表明一种涉及Der p3和Orai1通道的亚最大抑制的治疗可以抑制肥大细胞对屋尘螨的激活。我们的研究结果表明，Der p3是一种重要的空气过敏原，可以激活Ca2+通道，并为治疗螨虫诱发的哮喘提供了一种治疗策略。
The house dust mite is the principal source of perennial aeroallergens in man. How these allergens activate innate and adaptive immunity is unclear, and therefore, there are no therapies targeting mite allergens. Here, we show that house dust mite extract activates store-operated Ca2+channels, a common signaling module in numerous cell types in the lung. Activation of channel pore-forming Orai1 subunits by mite extract requires gating by STIM1 proteins. Although mite extract stimulates both protease-activated receptor type 2 (PAR2) and PAR4 receptors, Ca2+influx is more tightly coupled to the PAR4 pathway. We identify a major role for the serine protease allergen Der p3 in stimulating Orai1 channels and show that a therapy involving sub-maximal inhibition of both Der p3 and Orai1 channels suppresses mast cell activation to house dust mite. Our results reveal Der p3 as an important aeroallergen that activates Ca2+channels and suggest a therapeutic strategy for treating mite-induced asthma.