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Signaling Mechanisms Intersecting Histamine Receptors and Pattern Recognition Receptor Activation in Dendritic Cells

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Being immune from allergy

A normally functioning immune system protects us from infection and is tolerant to innocuous environmental antigens but this is not the case in allergy and asthma patients. EU-funded investigators worked on determining the underlying mechanisms.

Health

Dendritic cells are important for ensuring apt immune responses. However, they are also key players in the initiation and maintenance of allergic inflammation. Histamine is a chemical released during allergic responses. The DC-SIGNAL (Signaling mechanisms intersecting histamine receptors and pattern recognition receptor activation in dendritic cells) project was initiated to elucidate the role of histamine in aberrant dendritic cell activation. Researchers determined that the histamine receptor 2 mediates dendritic cell response to microbial ligands in the presence of histamine. They also comprehensively characterised the associated intracellular signalling pathway. These results were published in top journals on allergy and asthma. Surprisingly, results showed that bacteria in the gastrointestinal tract secreted histamine. The scientists used a mouse model of respiratory allergy to decipher the role of histamine signalling. The histamine receptor 2-deficient animals developed a far more severe type of allergic inflammation due to defects in dendritic cell activation and lymphocyte regulation. Research outcomes have uncovered the importance of histamine activation of histamine receptor 2 for suppressing allergic inflammation and fine tuning immune responses. This has already resulted in five peer-reviewed publications, a book chapter, 25 oral communications and eight poster presentations. More manuscripts are currently under review for eventual publication. DC-SIGNAL findings are pivotal and have directed research towards testing the potential of histamine receptor 2 agonists to treat allergic airway inflammation. Project members also received funding to study the impact of bacterial-derived histamine on auto-immune conditions and inflammatory diseases such as asthma, food allergy and irritable bowel syndrome.

Keywords

Immune, allergy, asthma, dendritic cell, histamine, histamine receptor 2, agonist

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29 November 2022