| First Author | Bao C | Year | 2023 |
| Journal | Sci Immunol | Volume | 8 |
| Issue | 81 | Pages | eadc9417 |
| PubMed ID | 36930731 | Mgi Jnum | J:338987 |
| Mgi Id | MGI:7517265 | Doi | 10.1126/sciimmunol.adc9417 |
| Citation | Bao C, et al. (2023) A mast cell-thermoregulatory neuron circuit axis regulates hypothermia in anaphylaxis. Sci Immunol 8(81):eadc9417 |
| abstractText | 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. |
