Cytokine receptors commonly utilize Janus kinases (JAK) to activate effector cell programs, and different JAK inhibitors are in use for the treatment of a number of inflammatory disorders. JAK1 inhibition is also undergoing study for the treatment of asthma and atopic dermatitis (AD), as JAK1 gain-of-function mutations promote AD and asthma in patients. However, increasing evidence suggests that JAK1 signaling has tissue-specific properties that have an impact on particular diseases and affect therapeutic outcomes. A study in Cell used different genetic mouse models to show that although JAK1 promotes spontaneous skin inflammation in mice, its specific expression in vagal sensory neurons promotes immune homeostasis in the lung. The findings show that JAK1 expression in sensory neurons promotes Calcb expression, a gene encoding calcitonin gene-related peptide b, a neuropeptide linked to neuroinflammation, acting as a protection mechanism against allergen-induced inflammation. With data showing the anti-inflammatory role of JAK1 signaling in vagal sensory neurons in the lung, sensory neuromodulation can be a potential therapeutic approach to treat various inflammatory diseases.
Original reference: Tamari M. et al. Cell 187, 44-61 (2024)
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