The H1 histamine receptor regulates allergic lung responses

J Clin Invest. 2006 Jun;116(6):1624-32. doi: 10.1172/JCI26150. Epub 2006 May 4.

Abstract

Histamine, signaling via the type 1 receptor (H1R), has been shown to suppress Th2 cytokine production by in vitro cultured T cells. We examined the role of H1R in allergic inflammation in vivo using a murine asthma model. Allergen-stimulated splenic T cells from sensitized H1R-/- mice exhibited enhanced Th2 cytokine production. Despite this Th2 bias, allergen-challenged H1R-/- mice exhibited diminished lung Th2 cytokine mRNA levels, airway inflammation, goblet cell metaplasia, and airway hyperresponsiveness (AHR). Restoration of pulmonary Th2 cytokines in H1R-/- mice by intranasal IL-4 or IL-13 restored inflammatory lung responses and AHR. Further investigation revealed that histamine acts as a T cell chemotactic factor and defective T cell trafficking was responsible for the absence of lung inflammation. Cultured T cells migrated in response to histamine in vitro, but this was ablated by blockade of H1R but not H2R. In vivo, allergen-specific WT but not H1R-/- CD4+ T cells were recruited to the lungs of naive recipients following inhaled allergen challenge. H1R-/- T cells failed to confer airway inflammation or AHR observed after transfer of WT T cells. Our data establish a role for histamine and H1R in promoting the migration of Th2 cells into sites of allergen exposure.

Publication types

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

MeSH terms

  • Administration, Intranasal
  • Animals
  • Cell Movement
  • Cytokines / immunology
  • Disease Models, Animal
  • Histamine / immunology*
  • Interleukin-13 / administration & dosage
  • Interleukin-13 / immunology
  • Interleukin-4 / administration & dosage
  • Interleukin-4 / immunology
  • Lung / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin / immunology
  • Receptors, Histamine H1 / genetics
  • Receptors, Histamine H1 / immunology*
  • Respiratory Hypersensitivity / immunology*
  • T-Lymphocytes / immunology
  • Th2 Cells / immunology

Substances

  • Cytokines
  • Interleukin-13
  • Receptors, Histamine H1
  • Interleukin-4
  • Histamine
  • Ovalbumin