Cutting edge: histamine receptor H4 activation positively regulates in vivo IL-4 and IFN-gamma production by invariant NKT cells.
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.
Leite-de-Moraes
Maria C
MC
Faculté de Médecine René Descartes, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8147, Hôpital Necker, Paris, France. leite.de.moraes@necker.fr
Diem
Séverine
S
Michel
Marie-Laure
ML
Ohtsu
Hiroshi
H
Thurmond
Robin L
RL
Schneider
Elke
E
Dy
Michel
M
D000818:Animals; D003432:Cross-Linking Reagents / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D014644:Genetic Variation / Q000276:immunology; D006632:Histamine / Q000008:administration & dosage / Q000172:deficiency; D006640:Histidine Decarboxylase / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011968:Receptors, Histamine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000074040:Receptors, Histamine H4
D003432:Cross-Linking Reagents; C498829:Hrh4 protein, mouse; D011948:Receptors, Antigen, T-Cell; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D015847:Interleukin-4; D006632:Histamine; D007371:Interferon-gamma; D006640:Histidine Decarboxylase