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 BrombacherChyi Song Hsieh, Robert W. Gereau, Mark J. Miller, Zhou Feng Chen, Hongzhen Hu, Steve Davidson, Qin Liu, Brian S. Kim

Research output: Contribution to journalArticlepeer-review

352 Scopus citations

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.

Original languageEnglish
Pages (from-to)217-228.e13
JournalCell
Volume171
Issue number1
DOIs
StatePublished - Sep 21 2017

Keywords

  • IL-13
  • IL-4
  • IL-4Rα
  • JAK1
  • atopic dermatitis
  • itch
  • pruriceptor
  • pruritus
  • type 2 cytokines

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