Periostin Activation of Integrin Receptors onSensory Neurons Induces Allergic Itch
A ativação da periostina dos receptores da integrina nos neurônios sensoriais induzindo prurido alérgico
Santosh K. Mishra, Joshua J. Wheeler, Saumitra Pitake,Huiping Ding, Changyu Jiang, Tomoki Fukuyama, Judy S. Paps, Patrick Ralph, Jacob Coyne, Michelle Parkington, Jennifer DeBrecht, Lauren C. Ehrhardt-Humbert, Glenn P. Cruse, Wolfgang Ba ̈umer, Ru-Rong Ji, Mei-Chuan Ko, Thierry Olivr
Chronic allergic itch is a common symptom affectingmillions of people and animals, but its pathogenesisis not fully explained. Herein, we show that periostin,abundantly expressed in the skin of patients withatopic dermatitis (AD), induces itch in mice, dogs,and monkeys. We identify the integrinaVb3expressed on a subset of sensory neurons as theperiostin receptor. Using pharmacological and ge-netic approaches, we inhibited the function ofneuronal integrinaVb3, which significantly reducesperiostin-induced itch in mice. Furthermore, weshow that the cytokine TSLP, the application of AD-causing MC903 (calcipotriol), and house dust mitesall induce periostin secretion. Finally, we establishthat the JAK/STAT pathway is a key regulator ofperiostin secretion in keratinocytes. Altogether, ourresults identify a TSLP-periostin reciprocal activationloop that links the skin to the spinal cord via periph-eral sensory neurons, and we characterize the non-canonical functional role of an integrin in itch.