Humanized mouse model of mast cell-mediated passive cutaneous anaphylaxis and passive systemic anaphylaxis.
Humanized mouse model of mast cell-mediated passive cutaneous anaphylaxis and passive systemic anaphylaxis.
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DOI：
10.1016/j.jaci.2016.01.049
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发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Brehm MA
中科院分区：
文献类型：
--
作者：
Bryce PJ;Falahati R;Kenney LL;Leung J;Bebbington C;Tomasevic N;Krier RA;Hsu CL;Shultz LD;Greiner DL;Brehm MA
肥大细胞是人类过敏反应的关键组成部分，迫切需要允许在体内研究其对过敏反应的贡献和评估新的人类特异性疗法的动物模型。我们已经开发了一种新的人源化小鼠模型，支持人肥大细胞移植和人IgE依赖性过敏反应。该模型基于移植有人胸腺、肝和造血干细胞（称为BLT）的NOD-scid IL 2 γ SCF/GM-CSF/IL 3（NSG-SGM 3）小鼠品系。大量的人肥大细胞在NSG-SGM 3 BLT小鼠中发育，并聚集在免疫系统、腹膜腔和外周组织中。NSG-SGM 3 BLT小鼠中的人肥大细胞与原代人肥大细胞表型相似，并表达CD 117、类胰蛋白酶和FcεRI。这些肥大细胞以IgE依赖性和非依赖性的方式进行脱粒，并且可以容易地在体外培养用于另外的研究。用含有人恒定区的嵌合IgE对移植的NSG-SGM 3小鼠进行皮内致敏，导致产生了强烈的被动皮肤过敏反应（PCA）反应。此外，我们描述了人类肥大细胞抗原依赖性被动全身过敏反应（PSA）在致敏小鼠的第一份报告。NSG-SGM 3 BLT小鼠为肥大细胞生物学的研究提供了一种容易获得的人肥大细胞来源，并提供了PCA和PSA的临床前模型，可用于研究人过敏反应的发病机制，并在其进入临床之前测试新的治疗方法。免疫移植的NSG-SGM 3 BLT小鼠产生大量的人肥大细胞，并表现出强烈的被动皮肤过敏反应（PCA）和被动全身过敏反应（PSA）
Mast cells are a critical component of allergic responses in humans, and animal models that allow the in vivo investigation of their contribution to allergy and evaluation of new human-specific therapeutics are urgently needed. We have developed a new humanized mouse model that supports human mast cell engraftment and human IgE-dependent allergic responses. This model is based on the NOD-scid IL2rgnull SCF/GM-CSF/IL3 (NSG-SGM3) strain of mice engrafted with human thymus, liver and hematopoietic stem cells (termed BLT). Large numbers of human mast cells develop in NSG-SGM3 BLT mice and populate the immune system, peritoneal cavity, and peripheral tissues. The human mast cells in NSG-SGM3 BLT mice are phenotypically similar to primary human mast cells and express CD117, tryptase, and FcεRI. These mast cells undergo degranulation in an IgE-dependent and independent manner, and can be readily cultured in vitro for additional studies. Intradermal priming of engrafted NSG-SGM3 mice with a chimeric IgE containing human constant regions resulted in development of a robust passive cutaneous anaphylaxis (PCA) response. Moreover, we describe the first report of a human mast cell antigen-dependent passive systemic anaphylaxis (PSA) response in primed mice. NSG-SGM3 BLT mice provide a readily available source of human mast cells for investigation of mast cell biology and a pre-clinical model of PCA and PSA that can be used to investigate the pathogenesis of human allergic responses and to test new therapeutics prior to their advancement to the clinic. Immune engrafted NSG-SGM3 BLT mice generate high numbers of human mast cells and exhibit robust passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis reactions (PSA)
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影响因子：
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