A basophil-neuronal axis promotes itch

Cell. 2021 Jan 21;184(2):422-440.e17. doi: 10.1016/j.cell.2020.12.033. Epub 2021 Jan 14.

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: IgE; allergy; atopic dermatitis; basophils; itch; leukotriene; mast cells; pruritus; sensory neurons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Allergens / immunology
  • Animals
  • Basophils / pathology*
  • Chronic Disease
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / pathology
  • Disease Models, Animal
  • Histamine / metabolism
  • Humans
  • Immunoglobulin E / immunology
  • Inflammation / pathology
  • Leukotrienes / metabolism
  • Mast Cells / immunology
  • Mice, Inbred C57BL
  • Neurons / pathology*
  • Phenotype
  • Pruritus / immunology
  • Pruritus / pathology*
  • TRPA1 Cation Channel / metabolism
  • TRPV Cation Channels / metabolism

Substances

  • Allergens
  • Leukotrienes
  • TRPA1 Cation Channel
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Trpa1 protein, mouse
  • Immunoglobulin E
  • Histamine