Sensory neurons promote immune homeostasis in the lung. (https://pubmed.ncbi.nlm.nih.gov/38134932/)

These scientists wanted to understand how certain proteins called cytokines can cause diseases that involve long-term inflammation in our bodies. They focused on a specific protein called JAK1, which is involved in allergic inflammation, a condition that causes problems with our skin and lungs.

To study this, the scientists inserted a human version of the JAK1 protein that has a special change (called a gain-of-function variant) into mice. This change made the mice develop a skin disease similar to a condition called atopic dermatitis, which causes itchy and irritated skin. But, surprisingly, when the JAK1 protein was only present in a specific part of the body called the stroma, the mice became resistant to lung inflammation, which is a problem in asthma.

The scientists then discovered that the JAK1 protein has another important role in a part of our body called the vagal sensory neurons. These neurons are responsible for sensing things in our airways. They found that the JAK1 protein in these neurons helps to suppress airway inflammation, which is a good thing because it prevents problems like asthma.

Furthermore, the scientists found that the JAK1 protein is necessary for the production of a molecule called CGRPbeta in the vagus nerve. This molecule actually helps to suppress a type of immune cell and prevent allergic airway inflammation.

Overall, the scientists learned that the JAK1 protein has different functions in different parts of our body. It can cause skin problems but also help protect our airways from inflammation. This discovery suggests that in the future, medicines that target JAK1 could be made to work specifically in certain parts of our body, which would be very helpful for treating diseases more effectively.

Tamari M., Del Bel KL., Ver Heul AM., Zamidar L., Orimo K., Hoshi M., Trier AM., Yano H., Yang TL., Biggs CM., Motomura K., Shibuya R., Yu CD., Xie Z., Iriki H., Wang Z., Auyeung K., Damle G., Demircioglu D., Gregory JK., Hasson D., Dai J., Chang RB., Morita H., Matsumoto K., Jain S., Van Dyken S., Milner JD., Bogunovic D., Hu H., Artis D., Turvey SE., Kim BS. Sensory neurons promote immune homeostasis in the lung. Cell. 2024 Jan 4;187(1):44-61.e17. doi: 10.1016/j.cell.2023.11.027. Epub 2023 Dec 21.