Summary: Periostin directly activates sensory neurons linked to itch. Pharmacological or genetic blockade of the periostin receptor reduced itch behavior in mouse models of chronic allergic skin inflammation.

Periostin Links Skin Allergic Responses to Itch-Sensory Neurons

Source: North Carolina State University

Researchers at North Carolina State University report that periostin — a protein commonly upregulated in allergic skin conditions — can directly activate itch-associated sensory neurons in the skin. The team found that blocking the neuronal receptor for periostin reduced itch responses in a mouse model of atopic dermatitis (eczema). These findings clarify a direct molecular connection between skin inflammation and the nervous system and point toward potential new therapeutic targets for chronic allergic itch.

How Itch Signals Travel

Itch is transmitted from nerve endings in the skin to the central nervous system through sensory neurons whose cell bodies lie in the dorsal root ganglia (DRG), clusters of sensory cells located near the spinal cord. When an itch-related signal is initiated in the skin, these sensory neurons carry the signal to the spinal cord and then on to higher brain centers that produce the conscious sensation of itching.

Periostin Acts Directly on Sensory Neurons

In this study, Santosh Mishra, assistant professor of neuroscience at NC State, and collaborators identified a direct action of periostin on sensory neurons. Periostin is produced in large amounts by skin cells during allergic inflammation. The research team showed that periostin can bind to a receptor on a subset of sensory neurons and trigger the neuronal activity that leads to itch behavior.

Integrin αvβ3 Identified as the Periostin Receptor

Using a combination of pharmacological and genetic approaches, the investigators identified the integrin protein αvβ3 as the sensory neuronal receptor that mediates periostin’s itch-promoting effects. When the αvβ3 receptor was inhibited or genetically suppressed in their mouse model, periostin-induced itch responses were significantly reduced, demonstrating that this integrin plays a functional and noncanonical role in itch signaling.

Allergens, Cytokines, and Periostin Production

The group also showed that several stimuli associated with atopic dermatitis increase periostin secretion in the skin. These included the cytokine thymic stromal lymphopoietin (TSLP), household allergens such as dust mites, and application of agents that induce AD-like inflammation in mice. The findings indicate that periostin production in keratinocytes is part of the allergic skin response and that periostin acts as a downstream mediator connecting skin inflammation to sensory neurons.

Regulation and a Reciprocal Activation Loop

Mechanistically, data from the study implicate the JAK/STAT intracellular signaling pathway in the regulation of periostin secretion by keratinocytes. The authors propose a reciprocal activation loop in which TSLP stimulates periostin release from skin cells, and periostin in turn activates sensory neurons via αvβ3, thereby linking peripheral skin inflammation to the spinal cord and the central perception of itch.

Implications for Treatment of Chronic Allergic Itch

Chronic allergic itch is a widespread and debilitating symptom in conditions such as atopic dermatitis. By identifying a specific receptor-mediated connection between periostin and sensory neurons, this research highlights a potential therapeutic target. Interrupting the periostin–αvβ3 interaction, or modulating periostin production through pathways such as JAK/STAT, may offer strategies to reduce or prevent itch without broadly suppressing immune function.

While these results come from animal models and additional work is required to translate findings to human clinical practice, the study provides a clearer map of the earliest junction between inflamed skin and the nervous system in allergic itch. Targeting that junction could lead to more focused therapies that directly reduce the sensation of itch in patients with eczema and related conditions.

Publication and Funding

This research was published in Cell Reports. The work was supported in part by North Carolina State University startup funds. Santosh Mishra is listed as first and corresponding author of the paper.

About this neuroscience research article — North Carolina State University