Journal Club 2017. 11. 03.

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

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

Landon K. Oetjen,1,2 Madison R. Mack,1,2 Jing Feng,1,3 Timothy M. Whelan,1,2 Haixia Niu,1,2 Changxiong J. Guo,1,3
Sisi Chen,4 Anna M. Trier,1,2 Amy Z. Xu,1,2 Shivani V. Tripathi,1,2 Jialie Luo,1,3 Xiaofei Gao,1,3 Lihua Yang,5
Samantha L. Hamilton,5 Peter L. Wang,6 Jonathan R. Brestoff,6 M. Laurin Council,2 Richard Brasington,7
Andra ́ s Schaffer,2,6 Frank Brombacher,8 Chyi-Song Hsieh,6,7 Robert W. Gereau IV,3 Mark J. Miller,5 Zhou-Feng Chen,1,3 Hongzhen Hu,1,3 Steve Davidson,4 Qin Liu,1,3 and Brian S. Kim1,2,3,6,9,*
1Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO 63110, USA
2Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
3Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA
4Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
5Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA 6Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
7Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA 8International 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
9Lead Contact
*Correspondence: briankim@wustl.edu
http://dx.doi.org/10.1016/j.cell.2017.08.006

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 asso- ciated with chronic inflammatory diseases, including asthma and atopic dermatitis. However, the mecha- nisms 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-4Ra and JAK1 signaling. We also observe that patients with recalcitrant chronic itch that failed other immunosuppressive therapies mark- edly 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 para- digm in which the sensory nervous system employs classical immune signaling pathways to influence mammalian behavior.