@article{a6665a8cb2a64a2eb40c0711ba2f1167,
title = "Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch",
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",
author = "Oetjen, {Landon K.} and Mack, {Madison R.} and Jing Feng and Whelan, {Timothy M.} and Haixia Niu and Guo, {Changxiong J.} and Sisi Chen and Trier, {Anna M.} and Xu, {Amy Z.} and Tripathi, {Shivani V.} and Jialie Luo and Xiaofei Gao and Lihua Yang and Hamilton, {Samantha L.} and Wang, {Peter L.} and Brestoff, {Jonathan R.} and Council, {M. Laurin} and Richard Brasington and Andr{\'a}s Schaffer and Frank Brombacher and Hsieh, {Chyi Song} and Gereau, {Robert W.} and Miller, {Mark J.} and Chen, {Zhou Feng} and Hongzhen Hu and Steve Davidson and Qin Liu and Kim, {Brian S.}",
note = "Funding Information: We thank all our collaborators at Washington University School of Medicine (WUSM) for their advice and discussion. We also thank members of the Division of Dermatology at WUSM for their assistance with patient sample collection. Specifically, we thank Ms. Mary Tabacchi, Ms. Nancy Bodet, and Dr. Lynn Cornelius for their support. This publication was supported, in part, by a grant from LEO Pharma and by the WUSM Institute of Clinical and Translational Sciences ( ICTS ), which is supported by the NIH National Center for Advancing Translational Sciences ( NCATS ) Clinical and Translational Science Award (CTSA) ( UL1TR000448 ). We also thank the Genome Technology Access Center (GTAC) at WUSM for assistance with RNA sequencing. GTAC is partially supported by an NCI grant ( P30CA91842 ) and by an ICTS CTSA grant ( UL1TR000448 ) from the National Center for Research Resources ( NCRR ). We also thank the WUSM Alafi Neuroimaging Laboratory, supported by an NCRR Shared Instrumentation grant ( 1S10RR027552 ). We thank the WUSM Digestive Disease Research Core Center for histology assistance, supported by an NIDDK grant ( P30DK052574 ). We also thank the Immunomonitoring Laboratory (IML) at the Bursky Center for Human Immunology & Immunotherapy Programs (ChiiPs) for flow cytometry support. Research using human DRG in the Gereau Lab is supported by an NINDS grant ( R01NS042595 ). The Davidson Lab is supported by an NIAMS grant ( R21AR068012 ). The Hu Lab is supported by an NIGMS grant ( R01GM101218 ) and an NIDDK grant ( R01DK103901 ). The Kim Lab is supported by NIAMS grants ( K08AR065577 and R01AR070116 ), the American Skin Association , and the Doris Duke Charitable Foundation . L.K.O. is supported by an NHLBI grant ( T32HL007317 ). A.Z.X. is supported by the Howard Hughes Medical Institute ( HHMI ) Medical Fellows Program. IL-4Rα flox mice were kindly provided by Dr. Herbert (Skip) Virgin at WUSM and Dr. Ajay Chawla at University of California, San Francisco. We also thank Dr. Steven Saenz for critical discussions. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = sep,
day = "21",
doi = "10.1016/j.cell.2017.08.006",
language = "English",
volume = "171",
pages = "217--228.e13",
journal = "Cell",
issn = "0092-8674",
number = "1",
}