PMID- 33450207
OWN - NLM
STAT- MEDLINE
DCOM- 20210826
LR  - 20240226
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 184
IP  - 2
DP  - 2021 Jan 21
TI  - A basophil-neuronal axis promotes itch.
PG  - 422-440.e17
LID - S0092-8674(20)31755-4 [pii]
LID - 10.1016/j.cell.2020.12.033 [doi]
AB  - 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.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Wang, Fang
AU  - Wang F
AD  - Division of Dermatology, Department of Medicine, Washington University School of 
      Medicine, St. Louis, MO 63110, USA; Center for the Study of Itch and Sensory 
      Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA; 
      Department of Dermatology, The First Affiliated Hospital, Sun Yat-sen University, 
      Guangzhou, Guangdong 510080, China.
FAU - Trier, Anna M
AU  - Trier AM
AD  - Division of Dermatology, Department of Medicine, Washington University School of 
      Medicine, St. Louis, MO 63110, USA; Center for the Study of Itch and Sensory 
      Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
FAU - Li, Fengxian
AU  - Li F
AD  - Center for the Study of Itch and Sensory Disorders, Washington University School 
      of Medicine, St. Louis, MO 63110, USA; Department of Anesthesiology, Zhujiang 
      Hospital of Southern Medical University, Guangzhou, Guangdong 510282, China; 
      Department of Anesthesiology, Washington University School of Medicine, St. 
      Louis, MO 63110, USA.
FAU - Kim, Seonyoung
AU  - Kim S
AD  - Division of Infectious Diseases, Department of Internal Medicine, Washington 
      University School of Medicine, St. Louis, MO 63110, USA.
FAU - Chen, Zhen
AU  - Chen Z
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
FAU - Chai, Jiani N
AU  - Chai JN
AD  - Department of Pathology and Immunology, Washington University School of Medicine, 
      St. Louis, MO 63110, USA.
FAU - Mack, Madison R
AU  - Mack MR
AD  - Division of Dermatology, Department of Medicine, Washington University School of 
      Medicine, St. Louis, MO 63110, USA; Center for the Study of Itch and Sensory 
      Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
FAU - Morrison, Stephanie A
AU  - Morrison SA
AD  - Division of Dermatology, Department of Medicine, Washington University School of 
      Medicine, St. Louis, MO 63110, USA; Center for the Study of Itch and Sensory 
      Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
FAU - Hamilton, Jennifer D
AU  - Hamilton JD
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
FAU - Baek, Jinok
AU  - Baek J
AD  - Division of Dermatology, Department of Medicine, Washington University School of 
      Medicine, St. Louis, MO 63110, USA; Department of Dermatology, College of 
      Medicine, Gachon University, Incheon 21565, Korea.
FAU - Yang, Ting-Lin B
AU  - Yang TB
AD  - Division of Dermatology, Department of Medicine, Washington University School of 
      Medicine, St. Louis, MO 63110, USA; Center for the Study of Itch and Sensory 
      Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
FAU - Ver Heul, Aaron M
AU  - Ver Heul AM
AD  - Center for the Study of Itch and Sensory Disorders, Washington University School 
      of Medicine, St. Louis, MO 63110, USA; Division of Allergy and Immunology, 
      Department of Medicine, Washington University School of Medicine, St. Louis, MO 
      63110, USA.
FAU - Xu, Amy Z
AU  - Xu AZ
AD  - Division of Dermatology, Department of Medicine, Washington University School of 
      Medicine, St. Louis, MO 63110, USA; Center for the Study of Itch and Sensory 
      Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
FAU - Xie, Zili
AU  - Xie Z
AD  - Center for the Study of Itch and Sensory Disorders, Washington University School 
      of Medicine, St. Louis, MO 63110, USA; Department of Anesthesiology, Washington 
      University School of Medicine, St. Louis, MO 63110, USA.
FAU - Dong, Xintong
AU  - Dong X
AD  - The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School 
      of Medicine, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Johns 
      Hopkins University School of Medicine, Baltimore, MD 21205, USA.
FAU - Kubo, Masato
AU  - Kubo M
AD  - Laboratory for Cytokine Regulation, Center for Integrative Medical Science, RIKEN 
      Yokohama Institute, Yokohama 230-0045, Kanagawa Prefecture, Japan; Division of 
      Molecular Pathology, Research Institute for Biomedical Science, Tokyo University 
      of Science, Noda 278-0022, Chiba Prefecture, Japan.
FAU - Hu, Hongzhen
AU  - Hu H
AD  - Center for the Study of Itch and Sensory Disorders, Washington University School 
      of Medicine, St. Louis, MO 63110, USA; Department of Anesthesiology, Washington 
      University School of Medicine, St. Louis, MO 63110, USA.
FAU - Hsieh, Chyi-Song
AU  - Hsieh CS
AD  - Department of Pathology and Immunology, Washington University School of Medicine, 
      St. Louis, MO 63110, USA; Division of Rheumatology, Department of Internal 
      Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
FAU - Dong, Xinzhong
AU  - Dong X
AD  - The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School 
      of Medicine, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Johns 
      Hopkins University School of Medicine, Baltimore, MD 21205, USA.
FAU - Liu, Qin
AU  - Liu Q
AD  - Center for the Study of Itch and Sensory Disorders, Washington University School 
      of Medicine, St. Louis, MO 63110, USA; Department of Anesthesiology, Washington 
      University School of Medicine, St. Louis, MO 63110, USA.
FAU - Margolis, David J
AU  - Margolis DJ
AD  - Department of Dermatology, University of Pennsylvania Perelman School of 
      Medicine, Philadelphia, PA 19104, USA.
FAU - Ardeleanu, Marius
AU  - Ardeleanu M
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
FAU - Miller, Mark J
AU  - Miller MJ
AD  - Division of Infectious Diseases, Department of Internal Medicine, Washington 
      University School of Medicine, St. Louis, MO 63110, USA.
FAU - Kim, Brian S
AU  - Kim BS
AD  - Division of Dermatology, Department of Medicine, Washington University School of 
      Medicine, St. Louis, MO 63110, USA; Center for the Study of Itch and Sensory 
      Disorders, 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; Department of Anesthesiology, Washington University 
      School of Medicine, St. Louis, MO 63110, USA. Electronic address: 
      briankim@wustl.edu.
LA  - eng
GR  - K08 AR065577/AR/NIAMS NIH HHS/United States
GR  - R01 AR070116/AR/NIAMS NIH HHS/United States
GR  - R01 AR056755/AR/NIAMS NIH HHS/United States
GR  - R01 NS054791/NS/NINDS NIH HHS/United States
GR  - R01 AA027065/AA/NIAAA NIH HHS/United States
GR  - R01 AI077600/AI/NIAID NIH HHS/United States
GR  - P30 CA091842/CA/NCI NIH HHS/United States
GR  - R01 DK103901/DK/NIDDK NIH HHS/United States
GR  - F30 AI154912/AI/NIAID NIH HHS/United States
GR  - R01 AR070873/AR/NIAMS NIH HHS/United States
GR  - R01 AR069062/AR/NIAMS NIH HHS/United States
GR  - R01 AG060962/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210114
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Allergens)
RN  - 0 (Leukotrienes)
RN  - 0 (TRPA1 Cation Channel)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (TRPV1 protein, mouse)
RN  - 0 (Trpa1 protein, mouse)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 820484N8I3 (Histamine)
SB  - IM
CIN - Cell. 2021 Jan 21;184(2):294-296. PMID: 33482094
CIN - Sci Immunol. 2021 Feb 5;6(56):. PMID: 33547051
CIN - J Allergy Clin Immunol. 2021 Sep;148(3):708-709. PMID: 34147536
MH  - Acute Disease
MH  - Allergens/immunology
MH  - Animals
MH  - Basophils/*pathology
MH  - Chronic Disease
MH  - Dermatitis, Atopic/immunology/pathology
MH  - Disease Models, Animal
MH  - Histamine/metabolism
MH  - Humans
MH  - Immunoglobulin E/immunology
MH  - Inflammation/pathology
MH  - Leukotrienes/metabolism
MH  - Mast Cells/immunology
MH  - Mice, Inbred C57BL
MH  - Neurons/*pathology
MH  - Phenotype
MH  - Pruritus/immunology/*pathology
MH  - TRPA1 Cation Channel/metabolism
MH  - TRPV Cation Channels/metabolism
MH  - Mice
PMC - PMC7878015
MID - NIHMS1660838
OTO - NOTNLM
OT  - IgE
OT  - allergy
OT  - atopic dermatitis
OT  - basophils
OT  - itch
OT  - leukotriene
OT  - mast cells
OT  - pruritus
OT  - sensory neurons
COIS- Declaration of interests B.S.K. has served as a consultant for AbbVie, ABRAX 
      Japan, Almirall, AstraZeneca, Cara Therapeutics, Daewoong Pharmaceutical, Incyte, 
      LEO Pharma, Lilly, Maruho, Menlo Therapeutics, OM Pharma, Pfizer, and Third Rock 
      Ventures. He has also participated on the advisory board for Almirall, Boehringer 
      Ingelheim, Cara Therapeutics, Kiniksa Pharmaceuticals, Menlo Therapeutics, 
      Regeneron Pharmaceuticals, Sanofi Genzyme, and Trevi Therapeutics. He is 
      stockholder of Locus Biosciences. All other authors declare that they have no 
      relevant conflicts of interest.
EDAT- 2021/01/16 06:00
MHDA- 2021/08/27 06:00
PMCR- 2022/01/21
CRDT- 2021/01/15 20:09
PHST- 2020/05/21 00:00 [received]
PHST- 2020/10/09 00:00 [revised]
PHST- 2020/12/21 00:00 [accepted]
PHST- 2021/01/16 06:00 [pubmed]
PHST- 2021/08/27 06:00 [medline]
PHST- 2021/01/15 20:09 [entrez]
PHST- 2022/01/21 00:00 [pmc-release]
AID - S0092-8674(20)31755-4 [pii]
AID - 10.1016/j.cell.2020.12.033 [doi]
PST - ppublish
SO  - Cell. 2021 Jan 21;184(2):422-440.e17. doi: 10.1016/j.cell.2020.12.033. Epub 2021 
      Jan 14.