Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch.

Journal Article (Journal Article)

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 αVβ3 expressed on a subset of sensory neurons as the periostin receptor. Using pharmacological and genetic approaches, we inhibited the function of neuronal integrin αVβ3, 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.

Full Text

Duke Authors

Cited Authors

  • Mishra, SK; Wheeler, JJ; Pitake, S; Ding, H; Jiang, C; Fukuyama, T; Paps, JS; Ralph, P; Coyne, J; Parkington, M; DeBrecht, J; Ehrhardt-Humbert, LC; Cruse, GP; Bäumer, W; Ji, R-R; Ko, M-C; Olivry, T

Published Date

  • April 7, 2020

Published In

Volume / Issue

  • 31 / 1

Start / End Page

  • 107472 -

PubMed ID

  • 32268102

Pubmed Central ID

  • PMC9210348

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2020.03.036


  • eng

Conference Location

  • United States