The neuroimmune axis: Integrating two systems to decipher itch

An age-old question in the field of itch research is "why do we experience itch?" Though the physiological reason for acute itch may be clear in the setting of irritants or infections, the mechanisms of pathologic itch remain largely elusive. Ongoing research into the molecular and cellular drivers of chronic pruritus has revealed a palpable synergy between the nervous and immune systems. Classic immune signaling molecules directly activate sensory neurons to evoke itch, while neuropeptides concurrently modulate local immune responses. This bidirectional crosstalk between two widespread systems orchestrates the body's response to environmental stimuli. Here, we review how these neuroimmune interactions drive pathologic itch, with an emphasis on pruritic diseases and novel therapies modulating these pathways. We additionally discuss these mechanisms in the context of different tissues. Deciphering the intricacies of the neuroimmune network has already led to transformative therapies and may ultimately help us understand why we experience itch.