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Papers of the Week


Papers: 4 Apr 2020 - 10 Apr 2020


Animal Studies

PAIN TYPE:
Itch


2020 Apr 07


Cell Rep


31


1

Editor's Pick

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

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
Cell Rep. 2020 Apr 07; 31(1):107472.
PMID: 32268102.

Abstract

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 αβ3 expressed on a subset of sensory neurons as the periostin receptor. Using pharmacological and genetic approaches, we inhibited the function of neuronal integrin αβ3, 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.