Chronic allergic itch is a common symptom affecting millions of people and animals, but its pathogenesis is not fully explained. Herein, we show that periostin, abundantly expressed in the skin of patients with atopic dermatitis (AD), induces itch in mice, dogs, and monkeys. We identify the integrin α_Vβ3 expressed on a subset of sensory neurons as the periostin receptor. Using pharmacological and genetic approaches, we inhibited the function of neuronal integrin α_Vβ3, which significantly reduces periostin-induced itch in mice. Furthermore, we show that the cytokine TSLP, the application of AD-causing MC903 (calcipotriol), and house dust mites all induce periostin secretion. Finally, we establish that the JAK/STAT pathway is a key regulator of periostin secretion in keratinocytes. Altogether, our results identify a TSLP-periostin reciprocal activation loop that links the skin to the spinal cord via peripheral sensory neurons, and we characterize the non-canonical functional role of an integrin in itch.

慢性过敏性瘙痒是影响数百万人和动物的常见症状，但其发病机制尚不完全清楚。在这里，我们表明在特应性皮炎 (AD) 患者的皮肤中大量表达的骨膜素会在小鼠、狗和猴子中引起瘙痒。我们将在感觉神经元子集上表达的整合素 α _{V β3 鉴定为骨膜素受体。}使用药理学和遗传学方法，我们抑制了神经元整合素 α _V的功能β3，显着减少骨膜素引起的小鼠瘙痒。此外，我们发现细胞因子 TSLP、引起 AD 的 MC903（卡泊三醇）和屋尘螨的应用都会诱导骨膜素分泌。最后，我们确定 JAK/STAT 通路是角质形成细胞中骨膜素分泌的关键调节因子。总而言之，我们的结果确定了一个 TSLP-periostin 相互激活环，该环通过外周感觉神经元将皮肤与脊髓连接起来，并且我们描述了整合素在瘙痒中的非规范功能作用。