Publikationsdatenbank

Periostin activation of integrin receptors on sensory neurons induces allergic itch (2020)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Mishra, Santosh K.

Wheeler, Joshua J.

Pitake, Saumitra

Ding, Huiping

Jiang, Changyu

Fukuyama, Tomoki

Paps, Judy S.

Ralph, Patrick

Coyne, Jacob

Parkington, Michelle

DeBrecht, Jennifer

Ehrhardt-Humbert, Lauren C.

Cruse, Glenn P.

Bäumer, Wolfgang (WE 14)

Ji, Ru-Rong

Ko, Mei-Chuan

Olivry, Thierry

Quelle

Cell reports

Bandzählung: 31

Heftzählung: 1

Seiten: 107472

ISSN: 2211-1247

Sprache

Englisch

Verweise

URL (Volltext): https://www.sciencedirect.com/science/article/pii/S2211124720303508

DOI: 10.1016/j.celrep.2020.03.036

Pubmed: 32268102

Kontakt

Institut für Pharmakologie und Toxikologie

Koserstr. 20
14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.