Mast Cell/Basophil-Nerve Crosstalk: Autonomic Signals and Sensory Circuits

Mast cells and basophils both contain basophilic granules and express the high-affinity immunoglobulin E (IgE) receptor FcεRI, but they are functionally distinct immune effectors. Mast cells are key effectors in the immediate phase of IgE-mediated allergy, while basophils contribute to the amplification and maintenance of type 2 inflammation through the production of type 2 cytokines, particularly interleukin-4 (IL-4) and IL-13. Both lineages express receptors for neurotransmitters and neuropeptides, and their activation thresholds and effector profiles are modulated by neuronal mediators. Psychological stress, through autonomic outflow and endocrine axes, increases the secretion of catecholamines and glucocorticoids, which act directly on mast cells and basophils to modulate degranulation, lipid mediator synthesis, and cytokine and chemokine secretion. In addition, mediators released from these cells, including histamine, proteases, lipid mediators, and cytokines, act on peripheral sensory neurons to cause itch and neurogenic inflammation. These bidirectional loops in barrier tissues constitute a neuroimmune interface that integrates environmental stress with immune reactivity. In this review, we synthesize the current evidence regarding mast cell/basophil receptor repertoires for autonomic and sensory mediators, delineate the directionality and kinetics of signaling between nerves and these effector cells, and highlight points of divergence between mast cells and basophils. We conclude with a description of the mechanistic frameworks linking stress, neuroimmune crosstalk, and disease exacerbation, and propose strategies for the development of targeted interventions.