Decoding the neuroimmune axis in the atopic march: mechanisms and implications

The immune and nervous systems have co-evolved complex mechanisms to sense environmental dangers and orchestrate a concerted response to safeguard tissue and mobilize host defenses. This sophisticated interplay, marked by a shared repertoire of receptors and ligands, influences disease pathogenesis. Neuro-immune interactions in allergic diseases are pivotal for symptom development, from anaphylaxis to chronic conditions like asthma and atopic dermatitis. This review explores the neuro-immune interplay within the atopic march, emphasizing its role in host defense, inflammation resolution, and tissue repair. We delve into the multifaceted functions of nociceptors in orchestrating type 2 immune responses and the progression of allergic disorders, focusing on key regulators such as CGRP-RAMP1 and SP-MRGPRB2/A2. Additionally, we discuss the potential of nociceptor neuron-blocking drugs to target neuro-immunity, offering the possibility of reversing the progression of the atopic march. Altogether, we underscore the need for targeted interventions to disrupt the pathological processes and enhance therapeutic outcomes at various stages of the atopic march.