A basophil-neuronal axis promotes itch

Fang Wang, Anna M. Trier, Fengxian Li, Seonyoung Kim, Zhen Chen, Jiani N. Chai, Madison R. Mack, Stephanie A. Morrison, Jennifer D. Hamilton, Jinok Baek, Ting Lin B. Yang, Aaron M. Ver Heul, Amy Z. Xu, Zili Xie, Xintong Dong, Masato Kubo, Hongzhen Hu, Chyi Song Hsieh, Xinzhong Dong, Qin LiuDavid J. Margolis, Marius Ardeleanu, Mark J. Miller, Brian S. Kim

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)422-440.e17
JournalCell
Volume184
Issue number2
DOIs
StatePublished - Jan 21 2021

Keywords

  • IgE
  • allergy
  • atopic dermatitis
  • basophils
  • itch
  • leukotriene
  • mast cells
  • pruritus
  • sensory neurons

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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