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. Additionally, we identified the neuronal receptor that is the initial connection between periostin and itch response."
Santosh Mishra, assistant professor of neuroscience at NC State and lead author of a paper on the work
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.
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."
l integrin αvβ3, which significantly reduced periostin-induced itch in mice. Furthermore, we showed that the cytokine TSLP, and the application of the AD-causing MC903 (calcipotriol) and house dust mites, all induced periostin secretion. Finally, we established that the JAK/STAT pathway is a key regulator of periostin secretion in keratinocytes. Altogether, our results identified a TSLP-periostin reciprocal activation loop that links the skin to the spinal cord via peripheral sensory neurons, and we characterized the non-canonical functional role of an integrin in itch.
Mishra, S.K., et al. (2020) Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch. Cell Reports. doi.org/10.1016/j.celrep.2020.03.036.