Individuals with germline JAK1 gain-of-function (GoF) variants develop atopic dermatitis and asthma. In Cell, Tamari et al. investigated the mechanism by which JAK1 signaling contributes to allergic inflammation, and identified a role for neuronal JAK1 in regulating neuropeptide expression in the vagal ganglia, which can suppress pathogenic ILC2 responses in the lung. Mice expressing the mutant human JAK1 GoF variant developed spontaneous atopic dermatitis-like disease, but spontaneous inflammation in the lung did not occur. Using a bone marrow chimera approach, the authors found that stromal expression of JAK1 GoF conferred resistance to lung inflammation. To investigate the involvement of sensory neurons in allergic lung inflammation, the researchers chemically denervated mice and found that this exacerbated inflammation. Sensory neurons from the vagal ganglia expressed Jak1, and conditional knockout of the Jak1 gene resulted in increased allergic lung inflammation. The expression of Calcb (which encodes the CGRPβ neuropeptide) was dependent on neuronal JAK1 expression, and CGRPβ was found to suppress ILC2 function and allergic airway inflammation. Together, the authors suggest that JAK1 regulates CGRPβ in sensory neurons and promotes immune homeostasis in the lung.

具有种系JAK1功能获得性 (GoF) 变异的个体会出现特应性皮炎和哮喘。在《细胞》中，Tamari 等人。研究了 JAK1 信号传导导致过敏性炎症的机制，并确定了神经元 JAK1 在调节迷走神经节神经肽表达中的作用，迷走神经节可以抑制肺部致病性 ILC2 反应。表达突变型人类JAK1 GoF 变体的小鼠出现了自发性特应性皮炎样疾病，但肺部并未发生自发性炎症。使用骨髓嵌合体方法，作者发现JAK1 GoF 的基质表达赋予对肺部炎症的抵抗力。为了研究感觉神经元在过敏性肺部炎症中的参与，研究人员对小鼠进行化学去神经，发现这会加剧炎症。迷走神经节的感觉神经元表达Jak1，条件性敲除Jak1基因会导致过敏性肺部炎症增加。Calcb （编码 CGRPβ 神经肽）的表达依赖于神经元 JAK1 的表达，并且发现 CGRPβ 可以抑制 ILC2 功能和过敏性气道炎症。作者认为 JAK1 调节感觉神经元中的 CGRPβ 并促进肺部的免疫稳态。