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Cell. 2017 Sep 21;171(1):217-228.e13. doi: 10.1016/j.cell.2017.08.006. Epub 2017 Sep 7.

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

Author information

1
Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
3
Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
4
Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
5
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
6
Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
7
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
8
Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
9
International Centre for Genetic Engineering and Biotechnology and Institute of Infectious Disease and Molecular Medicine, Division of Immunology, University of Cape Town, Cape Town 7700, South Africa.
10
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
11
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
12
Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: briankim@wustl.edu.

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.

KEYWORDS:

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

PMID:
28890086
PMCID:
PMC5658016
DOI:
10.1016/j.cell.2017.08.006
[Indexed for MEDLINE]
Free PMC Article

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