Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch

Landon K. Oetjen, Madison R. Mack, Jing Feng, Timothy M. Whelan, Haixia Niu, Changxiong J. Guo, Sisi Chen, Anna M. Trier, Amy Z. Xu, Shivani V. Tripathi, Jialie Luo, Xiaofei Gao, Lihua Yang, Samantha L. Hamilton, Peter L. Wang, Jonathan R. Brestoff, M. Laurin Council, Richard Brasington, András Schaffer, Frank Brombacher, Chyi-Song Hsieh, Robert W. Gereau IV, Mark J. Miller, Zhou-Feng Chen, et.al: 2017 Cell, Volume 171, Issue 1, p217–228.e13 Read More

Abstract

Mammals have evolved neurophysiologic reflexes, such as coughing and scratching, to expel invading pathogens and noxious environmental stimuli. It is well established that these responses are also associated with chronic inflammatory diseases, including 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 activate sensory neurons in both mice and humans. Further, we demonstrate that chronic itch is dependent on neuronal IL-4Rα and JAK1 signaling. We also observe that patients with recalcitrant chronic itch that failed other immunosuppressive therapies markedly improve when treated with JAK inhibitors. Thus, signaling mechanisms previously ascribed to the immune system may represent novel therapeutic targets within the nervous system. Collectively, this study reveals an evolutionarily conserved paradigm in which the sensory nervous system employs classical immune signaling pathways to influence mammalian behavior. © 2017 Elsevier Inc.

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Posted on October 24, 2017
Posted in: Axon Injury & Repair, HPAN, Neurodegeneration, Neurogenetics & Transcriptomics, Publications Authors: ,