Division for Cellular Immunology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Im Neuenheimer Feld 234, 69120 Heidelberg, Germany.
Division for Cellular Immunology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Division of Theoretical Systems Biology, German Cancer Research Center, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany.
Immunity. 2020 Feb 18;52(2):404-416.e5. doi: 10.1016/j.immuni.2020.01.012. Epub 2020 Feb 11.
Mast cells are rare tissue-resident cells of importance to human allergies. To understand the structural basis of principle mast cell functions, we analyzed the proteome of primary human and mouse mast cells by quantitative mass spectrometry. We identified a mast-cell-specific proteome signature, indicative of a unique lineage, only distantly related to other immune cell types, including innate immune cells. Proteome comparison between human and mouse suggested evolutionary conservation of core mast cell functions. In addition to specific proteases and proteins associated with degranulation and proteoglycan biosynthesis, mast cells expressed proteins potentially involved in interactions with neurons and neurotransmitter metabolism, including cell adhesion molecules, ion channels, and G protein coupled receptors. Toward targeted cell ablation in severe allergic diseases, we used MRGPRX2 for mast cell depletion in human skin biopsies. These proteome analyses suggest a unique role of mast cells in the immune system, probably intertwined with the nervous system.
肥大细胞是人体过敏反应中重要的罕见组织驻留细胞。为了了解主要肥大细胞功能的结构基础，我们通过定量质谱分析了原代人和鼠肥大细胞的蛋白质组。我们鉴定出了一个肥大细胞特异性蛋白质组特征，表明其具有独特的谱系，与其他免疫细胞类型（包括先天免疫细胞）仅有微弱的亲缘关系。人肥大细胞和鼠肥大细胞之间的蛋白质组比较表明核心肥大细胞功能具有进化保守性。除了与脱颗粒和蛋白聚糖生物合成相关的特定蛋白酶和蛋白质外，肥大细胞还表达了可能与神经元和神经递质代谢相互作用的蛋白质，包括细胞粘附分子、离子通道和 G 蛋白偶联受体。为了在严重过敏疾病中进行靶向细胞消融，我们在人皮肤活检中使用 MRGPRX2 进行肥大细胞耗竭。这些蛋白质组分析表明肥大细胞在免疫系统中具有独特的作用，可能与神经系统交织在一起。
