The CysLT 2 R receptor mediates leukotriene C 4 -driven acute and chronic itch

Significance Interactions between the nervous system and immune system are central regulators of chronic itch, a key feature of pathologies like atopic dermatitis and allergic contact dermatitis. Cysteinyl leukotrienes (LTC 4 , LTD 4 , and LTE 4 ) are eicosanoid lipids known for mediating inflammation, bronchoconstriction, and vascular leakage. We demonstrate here that CysLTs are potent itch inducers and that this effect depends on the specific coupling of LTC 4 with its receptor CysLT 2 R, which is expressed in a population of peripheral sensory neurons in the mouse and in human. We show that the LTC 4 /CysLT 2 R pathway contributes to a model of chronic itch, suggesting that CysLT 2 R could be a new therapeutic target for intractable chronic itch.