期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 116, 期 6, 页码 1624-1632出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI26150
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资金
- NIAID NIH HHS [R01 AI054471, R01 AI047417, 5R01AI054471] Funding Source: Medline
- NIAMS NIH HHS [R01 AR047417] Funding Source: Medline
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(-/-) 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.
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