2020.08.07 Journal club

Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch

Santosh K. Mishra,1,2,3,4,9,* Joshua J. Wheeler,1,2 Saumitra Pitake,1 Huiping Ding,5 Changyu Jiang,7 Tomoki Fukuyama,1 Judy S. Paps,8 Patrick Ralph,1 Jacob Coyne,1 Michelle Parkington,1 Jennifer DeBrecht,1 Lauren C. Ehrhardt-Humbert,1 Glenn P. Cruse,1,2 Wolfgang Ba ̈ umer,1,6 Ru-Rong Ji,7 Mei-Chuan Ko,5 and Thierry Olivry2,8
1Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA 2Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA

3The WM Keck Behavioral Center, North Carolina State University, Raleigh, NC, USA
4Program in Genetics, North Carolina State University, Raleigh, NC, USA
5Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA
6Institute of Pharmacology and Toxicology, Department of Veterinary Medicine, Freie Universita ̈ t Berlin, Berlin, Germany 7Duke University, Durham, NC, USA
8Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA 9Lead Contact
*Correspondence: skmishra@ncsu.edu

SUMMARY

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 aVb3 expressed on a subset of sensory neurons as the periostin receptor. Using pharmacological and ge- netic approaches, we inhibited the function of neuronal integrin aVb3, 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 periph- eral sensory neurons, and we characterize the non- canonical functional role of an integrin in itch.