한빛사 논문
Fang Wang1,2,3, Anna M. Trier1,2, Fengxian Li2,4,16, Seonyoung Kim5, Zhen Chen6, Jiani N. Chai7, Madison R. Mack1,2,17, Stephanie A. Morrison1,2, Jennifer D. Hamilton6, Jinok Baek1,8, Ting-Lin B. Yang1,2, Aaron M. Ver Heul2,9, Amy Z. Xu1,2, Zili Xie2,16, Xintong Dong10,11, Masato Kubo12,13, Hongzhen Hu2,16, Chyi-Song Hsieh7,14, Xinzhong Dong10,11, Qin Liu2,16, David J. Margolis15, Marius Ardeleanu6, Mark J. Miller5, Brian S. Kim1,2,7,16,18,*
1Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
2Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA
3Department of Dermatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China
4Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, China
5Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
6Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA
7Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
8Department of Dermatology, College of Medicine, Gachon University, Incheon 21565, Korea
9Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
10The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
11Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
12Laboratory for Cytokine Regulation, Center for Integrative Medical Science, RIKEN Yokohama Institute, Yokohama 230-0045, Kanagawa Prefecture, Japan
13Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, Noda 278-0022, Chiba Prefecture, Japan
14Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
15Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
16Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA
17Present address: Immunology and Inflammation Therapeutic Area, Sanofi, Cambridge, MA 02139, USA
18Lead contact
*Corresponding author
Abstract
Itch is an evolutionarily conserved sensation that facilitates expulsion of pathogens and noxious stimuli from the skin. However, in organ failure, cancer, and chronic inflammatory disorders such as atopic dermatitis (AD), itch becomes chronic, intractable, and debilitating. In addition to chronic itch, patients often experience intense acute itch exacerbations. Recent discoveries have unearthed the neuroimmune circuitry of itch, leading to the development of anti-itch treatments. However, mechanisms underlying acute itch exacerbations remain overlooked. Herein, we identify that a large proportion of patients with AD harbor allergen-specific immunoglobulin E (IgE) and exhibit a propensity for acute itch flares. In mice, while allergen-provoked acute itch is mediated by the mast cell-histamine axis in steady state, AD-associated inflammation renders this pathway dispensable. Instead, a previously unrecognized basophil-leukotriene (LT) axis emerges as critical for acute itch flares. By probing fundamental itch mechanisms, our study highlights a basophil-neuronal circuit that may underlie a variety of neuroimmune processes.
Keywords : allergy, atopic dermatitis, itch, pruritus, IgE, basophils, mast cells, leukotriene, sensory neurons
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