A new study has identified why some people feel itchy after a mosquito bite or exposure to allergens like dust or pollen, while others do not. Researchers at Massachusetts General Hospital have discovered the pathway by which immune and nerve cells interact to cause itching. By blocking this pathway in preclinical studies, they have suggested a new treatment approach for allergies. The findings were published in Nature and provide insights into why certain individuals are more likely to develop allergic responses than others.
Senior author Dr. Caroline Sokol explained that their research unveils a cellular and molecular circuit that controls allergen responsiveness, presenting a potential target for treating and preventing allergic reactions, including itching. The team’s preclinical data indicates that this approach could be translated into treatments for humans. When it comes to detecting pathogens like bacteria and viruses, the immune system is usually responsible. However, the sensory nervous system takes over when it comes to detecting allergens, leading to itchiness and allergic reactions.
The researchers had previously shown that the skin’s sensory nervous system, specifically neurons that cause itch, can directly detect allergens with protease activity. They suspected that innate immune cells might establish a threshold in sensory neurons for allergen reactivity, determining who is more likely to develop allergies. They discovered a poorly understood immune cell type in the skin, dubbed GD3 cells, that produce a molecule called IL-3 in response to environmental triggers, such as the skin’s natural microbes. IL-3 primes certain sensory neurons to be more reactive to allergens, making them more likely to trigger an allergic reaction.
Through various experiments in mouse models, the researchers found that removing IL-3 or GD3 cells, as well as blocking downstream signaling pathways, made the mice resistant to itch and immune responses triggered by allergens. This suggests that targeting the IL-3-mediated signaling pathway could lead to novel therapies for preventing allergies. The researchers believe that this pathway likely plays a similar role in human allergies and could provide new insights into allergic sensitization and prevention.
The study received funding from various sources, including the National Institutes of Health, Cure Alzheimer’s Fund, and the Massachusetts General Hospital Transformative Scholar Award. Dr. Sokol has received sponsored research support from GlaxoSmithKline and serves as a consultant for Bayer and Merck. The findings offer a new perspective on the relationship between immune and nerve cells in causing itching and allergic responses. By understanding the underlying mechanisms, researchers hope to develop targeted therapies that can prevent allergic reactions and provide relief to individuals who suffer from chronic itching and allergies.