Common protein in skin can ‘turn on’ allergic itch

Summary: Periostin can directly activate neurons associated with itching. Blocking periostin receptors reduced itch response in mouse models of chronic allergic itching.

Source: North Carolina State University

A commonly expressed protein in skin – periostin – can directly activate itch-associated neurons in the skin, according to new research from North Carolina State University. The researchers found that blocking periostin receptors on these neurons reduced the itch response in a mouse model of atopic dermatitis, or eczema. The findings could have implications for treatment of this condition..

Itch sensations are transmitted from neuronal projections in the skin through the dorsal root ganglia (DRG) – which are clusters of sensory cells located at the root of the spinal nerves – then to the spinal cord.

“We have found that periostin, a protein that is produced abundantly in skin as part of an allergic response, can interact directly with sensory neurons in the skin, effectively turning on the itch response,” says Santosh Mishra, assistant professor of neuroscience at NC State and lead author of a paper on the work. “Additionally, we identified the neuronal receptor that is the initial connection between periostin and itch response.”

Mishra and a team including colleagues from NC State, Wake Forest University and Duke University identified a receptor protein called αvβ3, which is expressed on sensory neurons in skin, as the periostin receptor.

This shows a woman scratching
Mishra and a team including colleagues from NC State, Wake Forest University and Duke University identified a receptor protein called αvβ3, which is expressed on sensory neurons in skin, as the periostin receptor. The image is in the public domain.

In a chemically-induced mouse model of atopic dermatitis, the team found that exposure to common allergens such as dust mites increased periostin production in skin, exacerbating the itch response. However, when the researchers “turned off” the receptor protein, itch was significantly reduced.

“Periostin and its receptor connect the skin directly to the central nervous system,” Mishra says. “We have identified the first junction in the itch pathway associated with eczema. If we can break that connection, we can relieve the itch.”

The research appears in Cell Reports, and was funded by NC State’s startup fund. Mishra is both first and corresponding author of the work.

About this neuroscience research article

Source:
North Carolina State University
Media Contacts:
Tracey Peake – North Carolina State University
Image Source:
The image is in the public domain.

Original Research: Open access
“Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch”. Santosh Mishra et al.
Cell Reports doi:10.1016/j.celrep.2020.03.036.

Abstract

Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch

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 genetic 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 ADcausing 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 noncanonical functional role of an integrin in itch.

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