Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Dermatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell. 2021 Jan 21;184(2):422-440.e17. doi: 10.1016/j.cell.2020.12.033. Epub 2021 Jan 14.
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，有助于将病原体和有害刺激物从皮肤中排出。然而，在器官衰竭、癌症和慢性炎症性疾病（如特应性皮炎）中，瘙痒会变成慢性、难治性和使人虚弱的。除了慢性瘙痒，患者通常还会经历强烈的急性瘙痒加剧。最近的发现揭示了瘙痒的神经免疫回路，从而开发出了抗瘙痒治疗方法。然而，急性瘙痒加剧的机制仍未被发现。在此，我们发现很大一部分特应性皮炎患者携带过敏原特异性免疫球蛋白 E (IgE)，并表现出急性瘙痒加剧的倾向。在小鼠中，虽然变应原引起的急性瘙痒在稳定状态下是由肥大细胞-组胺轴介导的，但与特应性皮炎相关的炎症使这种途径变得可有可无。相反，以前未被认识到的嗜碱性粒细胞-白三烯（LT）轴成为急性瘙痒加剧的关键。通过探究基本的瘙痒机制，我们的研究强调了一个嗜碱性粒细胞-神经元回路，它可能是多种神经免疫过程的基础。
