Cutting edge: histamine receptor H4 activation positively regulates in vivo IL-4 and IFN-gamma production by invariant NKT cells

J Immunol. 2009 Feb 1;182(3):1233-6. doi: 10.4049/jimmunol.182.3.1233.

Abstract

Histamine (HA) is a biogenic amine with multiple activities in the immune system. In this study we demonstrate that histamine-free histidine decarboxylase-deficient (HDC(-/-)) mice present a numerical and functional deficit in invariant NK T (iNKT) cells as evidenced by a drastic decrease of IL-4 and IFN-gamma production. This deficiency was established both by measuring cytokine levels in the serum and intracellularly among gated iNKT cells. It resulted from the lack of HA, because a single injection of this amine into HDC(-/-) mice sufficed to restore normal IL-4 and IFN-gamma production. HA-induced functional recovery was mediated mainly through the H4 histamine receptor (H4R), as assessed by its abrogation after a single injection of a selective H4R antagonist and the demonstration of a similar iNKT cell deficit in H4R(-/-) mice. Our findings identify a novel function of HA through its H4R and suggest that it might become instrumental in modulating iNKT cell functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cross-Linking Reagents / metabolism
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • Genetic Variation / immunology
  • Histamine / administration & dosage
  • Histamine / deficiency
  • Histidine Decarboxylase / deficiency
  • Histidine Decarboxylase / genetics
  • Histidine Decarboxylase / physiology
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / biosynthesis*
  • Interleukin-4 / antagonists & inhibitors
  • Interleukin-4 / biosynthesis*
  • Lymphocyte Count
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / metabolism*
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / deficiency
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Histamine / deficiency
  • Receptors, Histamine / genetics
  • Receptors, Histamine / metabolism*
  • Receptors, Histamine H4

Substances

  • Cross-Linking Reagents
  • Hrh4 protein, mouse
  • Receptors, Antigen, T-Cell
  • Receptors, G-Protein-Coupled
  • Receptors, Histamine
  • Receptors, Histamine H4
  • Interleukin-4
  • Histamine
  • Interferon-gamma
  • Histidine Decarboxylase