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

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2017 Sep 12

PMID 28890086

Citations 361

Authors

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

Andras Schaffer

Frank Brombacher

Chyi-Song Hsieh

Robert W Gereau 4th

Mark J Miller

Zhou-Feng Chen

Hongzhen Hu

Steve Davidson

Qin Liu

Brian S Kim

Affiliations

Soon will be listed here.

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.

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