A Basophil-Neuronal Axis Promotes Itch

Itch is an evolutionarily conserved sensation that facilitates expulsion of pathogens and noxious stimuli from the skin. However, in organ failure, cancer, and chronic inflammatory disorders like atopic dermatitis (AD), itch becomes chronic, intractable, and debilitating. In addition to chronic itch, patients often experience intense acute itch exacerbations. Recent seminal discoveries have unearthed the neuroimmune circuitry of itch, leading to the development of novel treatments. However, the mechanisms underlying acute itch exacerbations remain overlooked. Herein, we show that a subpopulation of patients with AD exhibit a distinct pattern of acute itch flares. In mice, we found that while acute itch is mediated by the classical mast cell-histamine axis in steady-state, AD-associated inflammation renders this pathway dispensable. Instead, a previously unrecognized basophil-leukotriene axis emerges as critical for acute itch flares. By probing fundamental itch mechanisms, our study highlights a novel basophil-neuronal circuit that may underlie a variety of neuroimmune processes.