Identification of a Neuronal Receptor Controlling Anaphylaxis

• mGluR7 and glutamate provide autoinhibition to peripheral histaminergic neurons
• mGluR7 ablation and thus faulty regulation of peripheral neurons causes anaphylaxis
• mGluR7 regulates excessive itch via neuronal transmission in central itch pathways
• mGluR7 regulates symptoms of anaphylaxis via communication with the immune system

SummaryAllergic reactions can in severe cases induce a state of circulatory shock referred to as anaphylaxis. Histamine, the primary mediator of this condition, is released from immune cells, and, therefore, anaphylaxis has so far been considered an immune system disorder. However, we here show that the glutamatergic receptor mGluR7, expressed on a subpopulation of both peripheral and spinal cord neurons, controls histamine-induced communication through calcium-dependent autoinhibition with implications for anaphylaxis. Genetic ablation of mGluR7, and thus altered regulation of histamine-sensing neurons, caused an anaphylaxis-like state in mGluR7−/− mice, which could be reversed by antagonizing signaling between neurons and mast cells but not by antagonizing a central itch pathway. Our findings demonstrate the vital role of nervous system control by mGluR7 in anaphylaxis and open up possibilities for preventive strategies for this life-threatening condition.

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