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 such as atopic dermatitis (AD), itch becomes chronic, intractable, and debilitating. In addition to chronic itch, patients often experience intense acute itch exacerbations. Recent discoveries have unearthed the neuroimmune circuitry of itch, leading to the development of anti-itch treatments. However, mechanisms underlying acute itch exacerbations remain overlooked. Herein, we identify that a large proportion of patients with AD harbor allergen-specific immunoglobulin E (IgE) and exhibit a propensity for acute itch flares. In mice, while allergen-provoked acute itch is mediated by the mast cell-histamine axis in steady state, AD-associated inflammation renders this pathway dispensable. Instead, a previously unrecognized basophil-leukotriene (LT) axis emerges as critical for acute itch flares. By probing fundamental itch mechanisms, our study highlights a basophil-neuronal circuit that may underlie a variety of neuroimmune processes.

瘙痒是一种进化上保守的感觉，有助于从皮肤排出病原体和有害刺激。然而，在器官衰竭、癌症和慢性炎症性疾病（如特应性皮炎 (AD)）中，瘙痒会变得慢性、顽固且令人衰弱。除了慢性瘙痒外，患者还经常经历剧烈的急性瘙痒恶化。最近的发现揭示了瘙痒的神经免疫回路，从而促进了止痒治疗的发展。然而，急性瘙痒加剧的机制仍然被忽视。在此，我们发现大部分 AD 患者含有过敏原特异性免疫球蛋白 E (IgE)，并表现出急性瘙痒的倾向。在小鼠中，虽然过敏原引起的急性瘙痒是由稳定状态下的肥大细胞-组胺轴介导的，但与 AD 相关的炎症使得该通路变得可有可无。相反，以前未被认识到的嗜碱性粒细胞-白三烯（LT）轴对于急性瘙痒发作至关重要。通过探索基本的瘙痒机制，我们的研究强调了可能是多种神经免疫过程基础的嗜碱性粒细胞神经元回路。