IgE-mediated anaphylaxis is an acute life-threatening systemic reaction to allergens, including certain foods and venoms. Anaphylaxis is triggered when blood-borne allergens activate IgE-bound perivascular mast cells (MCs) throughout the body, causing an extensive systemic release of MC mediators. Through precipitating vasodilatation and vascular leakage, these mediators are believed to trigger a sharp drop in blood pressure in humans and in core body temperature in animals. We report that the IgE/MC-mediated drop in body temperature in mice associated with anaphylaxis also requires the body’s thermoregulatory neural circuit. This circuit is activated when granule-borne chymase from MCs is deposited on proximal TRPV1 + sensory neurons and stimulates them via protease-activated receptor-1. This triggers the activation of the body’s thermoregulatory neural network, which rapidly attenuates brown adipose tissue thermogenesis to cause hypothermia. Mice deficient in either chymase or TRPV1 exhibited limited IgE-mediated anaphylaxis, and, in wild-type mice, anaphylaxis could be recapitulated simply by systemically activating TRPV1 + sensory neurons. Thus, in addition to their well-known effects on the vasculature, MC products, especially chymase, promote IgE-mediated anaphylaxis by activating the thermoregulatory neural circuit.

中文翻译：

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肥大细胞-体温调节神经元回路轴调节过敏反应中的体温过低


IgE 介导的过敏反应是对过敏原（包括某些食物和毒液）的急性危及生命的全身反应。当血源性过敏原激活全身 IgE 结合的血管周围肥大细胞 (MC) 时，会引发过敏反应，导致 MC 介质广泛全身释放。通过促进血管舒张和血管渗漏，这些介质被认为会引发人类血压和动物核心体温的急剧下降。我们报告说，与过敏反应相关的小鼠 IgE/MC 介导的体温下降也需要身体的温度调节神经回路。当来自 MC 的颗粒携带的食糜酶沉积在近端 TRPV1 上时，该电路被激活+感觉神经元并通过蛋白酶激活受体 1 刺激它们。这会触发人体体温调节神经网络的激活，从而迅速减弱棕色脂肪组织的生热作用，从而导致体温过低。缺乏食糜酶或 TRPV1 的小鼠表现出有限的 IgE 介导的过敏反应，并且在野生型小鼠中，只需全身激活 TRPV1 即可重现过敏反应+感觉神经元。因此，除了众所周知的对脉管系统的影响外，MC 产品，尤其是食糜酶，还可以通过激活体温调节神经回路促进 IgE 介导的过敏反应。