The H1 histamine receptor regulates allergic lung responses

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.

Effect of Both Ultraviolet B Irradiation and Histamine Receptor Function on Allergic Responses to an Inhaled Antigen

“…This supports the findings of Bryce et al (27) who proposed an elevated constitutive activation of T cells within the airways of H1RKO mice. In papain-sensitized H1RKO mice, levels of IL-4, but not IL-5, IL-10, and IFN-␥, were significantly increased.…”

“…This supports an earlier study in mice in which IFN-␥ production was suppressed when the H1R was deleted and the secretion of Th2 cytokines including IL-4 and IL-13 was enhanced (31). A similar bias in cytokine production was also observed in splenocytes of H1RKO mice in an OVA asthma model, suggesting that the deletion of the H1R resulted in a systemic Th2 phenotype upon Ag exposure (27).…”

“…Studies using H1RKO mice have suggested that Th1-driven responses are enhanced by the action of histamine binding to the histamine-1 receptor (31), and that histamine may act as a chemotactic factor to facilitate T cell migration to the site of Ag exposure (27). Because histamine is released from mast cells in the skin upon UV irradiation (28), the responses of H1RKO mice were therefore studied to determine 1) the effect of papain sensitization on potentially Th2-susceptible mice and 2) the role of the H1R in UVB-induced immunosuppression.…”

“…Histamine is involved in acute inflammatory processes and plays a role in the edema, vasodilation, contraction of smooth muscle, up-regulation of adhesion molecules and hypersecretion of mucus associated with the allergic asthmatic reaction (27). Additionally, histamine has also been described as a chemotactic factor, the effect of which may be inhibited by blockade of the H1R, leaving T cells unable to home to the sites of Ag exposure (27). UVB irradiation of skin results in degranulation of mast cells and the release of histamine (28).…”

Rôle de l’histamine et des récepteurs histaminiques dans la pathogenèse du paludisme

“…Un schéma illustrant notre vision du phénomène est représenté sur la Figure 2. Dans ce contexte, il a été rapporté que l'histamine est essentielle au recrutement des lymphocytes T CD4 + et CD8 + spécifiques de l'antigène [29]. De nombreuses études ont démontré le rôle essentiel de la molécule d'adhésion ICAM-1 dans la séquestration des globules rouges infectés, et par conséquent dans le développement de la pathogenèse du paludisme, notamment par l'utilisation de souris déficientes en ICAM-1, qui sont résistantes au neuropaludisme [30,33] …”