Have you ever wondered why some people scratch themselves incessantly after a mosquito bite, while others barely notice the sting? New research, conducted on mice, provides a potential answer, uncovering a crucial link between the immune system and our experience of itch.
Our skin is home to a vast network of sensory neurons, nerve cells that detect changes in the environment and trigger sensations like pain. When we encounter allergens, like mosquito saliva, these neurons alert the body, potentially triggering an itchy sensation. They also activate nearby immune cells, initiating an inflammatory response that manifests as swelling and redness.
Over time, repeated exposure to allergens can lead to chronic allergic inflammation, fundamentally altering the tissues involved. Immune cells responding to allergens can change the sensitivity of nerves, making them more or less likely to react to a substance.
Dr. Caroline Sokol, a professor of allergy and immunology at Harvard Medical School and Massachusetts General Hospital, explains, “We all have sensory neurons, so we can all feel itchy — but not all of us get allergies, even though we’re surrounded by the same allergens.” This raises a critical question: What determines which sensory neurons fire in response to allergens?
To investigate this, Dr. Sokol and her team exposed mice to papain, a chemical that triggers an itchy sensation, causing mice to scratch their skin. Different groups of mice in the study lacked specific immune cells. The research, published in the journal Nature, revealed that mice lacking a specific type of T cell, dubbed GD3 cells, did not scratch when exposed to papain.
The researchers then investigated how these GD3 cells influenced sensory nerve responses. They cultivated GD3 cells in the lab and treated them with a chemical that induced the release of signaling molecules called cytokines. These cytokine-containing liquids were then injected into mice with normal immune systems.
While the treatment itself did not trigger itchiness, it intensified the mice’s scratching responses to various allergens, including mosquito saliva. This suggested that a substance released by GD3 cells amplified nerve-induced itching.
By comparing chemicals secreted by GD3 cells with those from other immune cells in the skin, the researchers identified a unique factor: interleukin 3 (IL-3), a molecule known for regulating inflammation.
Their findings revealed that only certain sensory neurons responded to IL-3. These responsive neurons became more likely to trigger an itch, indicating that IL-3 “primes” neurons to react to allergens. Interestingly, when the researchers removed the genes for IL-3 or its receptors, or eliminated GD3 cells altogether, the mice could not mount an allergic response.
Through further experiments, the researchers concluded that IL-3 activates two distinct signals: one that promotes nerve-driven itching and another that controls the immune component of the allergic response.
Dr. Sokol emphasizes that by releasing IL-3, GD3 cells are “absolutely essential” in determining the threshold at which a sensory nerve will react to an allergen. This chain reaction involving IL-3 “may give us a new pathway to treat patients with chronic itch disorders,” she adds.
However, it’s important to note that this research was conducted on mice. While mouse immune cells share many similarities with their human counterparts, further research is necessary to understand whether and how human T cells react to IL-3.
This knowledge is crucial for translating these findings into effective itch treatments or predicting who might be at risk of allergies. Dr. Sokol concludes, “We all have that friend who doesn’t react to mosquito bites and the friend who looks horrific after a day outside. We believe [the IL-3 pathway] is determining that in real time, because when we look at mosquito bite-induced itch — and the allergic immune response that follows — we see that it is completely dependent on the cells in this pathway.”
This groundbreaking research offers a promising avenue for understanding and treating itch, a common and often debilitating symptom. With further investigation, we may one day have a better understanding of why some people are more susceptible to itch, and potentially develop new therapies to alleviate this uncomfortable sensation.
