BioProject

Mammals have evolved neurophysiologic reflexes such as coughing and scratching to expel invading pathogens and noxious environmental factors. More...

Mammals have evolved neurophysiologic reflexes such as coughing and scratching to expel invading pathogens and noxious environmental factors. It is well established that these responses are also associated with chronic inflammatory diseases such as asthma and atopic dermatitis. However, the mechanisms by which inflammatory pathways promote sensations such as itch remain poorly understood. Here, we show that type 2 cytokines directly stimulate sensory neurons in both mice and humans. Further, we demonstrate that chronic itch is dependent on neuronal IL-4Rα and JAK1 signaling. Based on these observations, we show that patients with recalcitrant chronic itch markedly improve when treated with JAK inhibitors in proof-of-concept clinical studies. Thus, signaling mechanisms previously ascribed to the immune system may represent novel therapeutic targets within the nervous system. Collectively, these studies reveal an evolutionarily conserved paradigm in which the sensory nervous system employs classical immune signaling pathways to influence mammalian behavior. Overall design: Ear skin from 6 NaV1.8+ Il4raF/F mice treated with MC903 compared to skin from 4 littermates treated with 1 nM topical calipotriol (MC903) daily for 12 days. Less...