Allergy (Copenhagen), 2017-12, Vol.72 (12), p.1925-1935
2017
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- Autor(en) / Beteiligte
- Titel
- Histamine receptor 2 modifies iNKT cell activity within the inflamed lung
- Ist Teil von
- Allergy (Copenhagen), 2017-12, Vol.72 (12), p.1925-1935
- Ort / Verlag
- Denmark: Blackwell Publishing Ltd
- Erscheinungsjahr
- 2017
- Quelle
- Wiley Online Library - AutoHoldings Journals
- Beschreibungen/Notizen
- Background Histamine is a key immunoregulatory mediator and can dampen proinflammatory responses via activation of histamine receptor 2 (H2R). The aim of this study was to determine the role of H2R in modulating lung inflammatory responses. Methods H2R was blocked using famotidine or activated using dimaprit in both the ovalbumin (OVA) and house dust mite extract (HDM) murine models of respiratory inflammation. H2R‐deficient animals and CD1d/H2R‐deficient animals were utilized to examine the CD1d presentation of lipid antigens (αGalCer or OCH) to invariant natural killer T (iNKT) cells. Results Famotidine treatment resulted in more severe airway disease in the OVA model, while dimaprit treatment significantly reduced disease severity. Both OVA and HDM‐induced airway diseases were more severe in H2R‐deficient animals. Flow cytometric analysis of lung tissue from H2R‐deficient animals revealed increased numbers of CD1d+ dendritic cells and increased numbers of iNKT cells. In vitro, αGalCer‐stimulated iNKT cells from H2R‐deficient mice secreted higher levels of IL‐4, IL‐5, and GM‐CSF. In vivo, αGalCer or OCH administration to the lung resulted in enhanced mucus secretion, inflammatory cell recruitment, and cytokine production in H2R‐deficient or famotidine‐treated animals, while dimaprit dampened the lung iNKT cell response to αGalCer. Removal of iNKT cells in H2R‐deficient (CD1d−/−H2R−/−) animals normalized the lung response to HDM. Conclusion The deliberate activation of H2R, or its downstream signaling molecules, may represent a novel therapeutic target for chronic lung inflammatory diseases, especially when CD1d‐mediated presentation of lipid antigens to iNKT cells is contributing to the pathology.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0105-4538eISSN: 1398-9995DOI: 10.1111/all.13227Titel-ID: cdi_proquest_miscellaneous_1910794503
- Format
- –
- Schlagworte
- Activation, allergy, Animal models, Animals, Antigen presentation, Antigens, Antigens, CD1d - metabolism, Biomarkers, CD1d, CD1d antigen, Dendritic cells, Disease Models, Animal, Disease Progression, Famotidine, Female, Flight corridors, Flow cytometry, Granulocyte-macrophage colony-stimulating factor, Histamine, House dust, Immunophenotyping, Immunoregulation, inflammation, Inflammation Mediators, Inflammatory diseases, Interleukin 4, Interleukin 5, invariant natural killer T cells, Lung diseases, Lungs, Lymphocyte Activation - immunology, Lymphocyte Count, Medical treatment, Mice, Mice, Knockout, Mucus, Natural killer cells, Natural Killer T-Cells - immunology, Natural Killer T-Cells - metabolism, Ovalbumin, Phenotype, Pneumonia - genetics, Pneumonia - immunology, Pneumonia - metabolism, Pneumonia - pathology, Receptors, Histamine H2 - genetics, Receptors, Histamine H2 - metabolism, Respiratory tract, Respiratory tract diseases, Rodents, Secretion, T-Lymphocyte Subsets - immunology, T-Lymphocyte Subsets - metabolism, T-Lymphocytes, Regulatory - immunology, T-Lymphocytes, Regulatory - metabolism