Researchers have identified how nerves in the skin play a role in the immune response to allergens, through the release of the neuropeptide Substance P. These findings, published online ahead of print in Immunity (Oct. 23, 2020), could lead to new and better ways to treat and prevent allergies, according to the authors.
In a press release, the investigators explain that while it has been known that dendritic cells (DCs) in the skin are involved in the allergic response by activating T-cells, how the DCs are triggered by allergen exposure has not been understood.
“Allergy-triggering dendritic cells are located next to allergen-responsive neurons in the skin. We found that when exposed to an allergen, these neurons release Substance P,” said Dr. Caroline Sokol lead author of the study, in the release. “Substance P then directly induces migration of those dendritic cells to the lymph nodes, where they, in turn, activate T cells. Those T cells then marshal the attack against the allergen invader.” Those allergic-response triggering dendritic cells are called CD301b+ Dcs.
Dr. Sokol is an investigator at Massachusetts General Hospital's Center for Immunology and Inflammatory Diseases.
Part of the insight that other cells in the skin were involved in the process came from comparing studies of cultured DCs in isolation to DCs in living systems.
“We saw that something was happening in living systems that does not happen in cultured dendritic cells,” Dr. Sokol said. “So we hypothesized that in living systems there must be some intermediate step between exposure to the allergen and activation of the dendritic cells.”
Studies in isolated cells, as well as in animal models, showed that sensory neurons could detect allergens. Dr. Sokol and her colleagues also demonstrated that CD301b+ DCs could be found close to sensory neurons in the skin. The investigators say that taken together, these findings suggested that sensory neurons play a major role in immune cell activation in response to allergens.
When the researchers tried chemically blocking allergy-sensing neurons in mice, they found they could interrupt the activation of an allergic response. They also showed that Substance P is released by allergen-activated neurons in both cultured cells and living systems and that Substance P, on its own, can activate the specific types of dendritic cells needed to, in turn, activate the T cells and complete the allergic response. Blocking sensory neuron function also inhibited the activation of T cells associated with the allergic response.
The researchers say their discovery not only broadens understanding of the immune system, but also opens new avenues for the development of therapies to treat allergies.
“This sensory-neuron-dependent pathway, and Substance P, are necessary to trigger an immune response to allergens,” said Dr. Sokol. “If we can interrupt that we can possibly stop the allergic immune response.”