H₄ receptors in mast cells and basophils: A new therapeutic target for allergy?

It has long been recognised that mast cells and basophils are prominent sources of preformed histamine in humans and that this biogenic amine serves as one of the most important inflammatory mediators. In allergic diseases, histamine has previously been shown to partially modulate symptoms such as airway obstruction, mucus secretion, reddening of the skin and itch, all of which were attributed to engagement of H₁-receptors with the amine. However, more recently it has been shown that certain key biological functions of histamine, such as itch, are also crucially controlled by H ₄-receptor stimulation, resulting in a growing interest in combinational anti-H₁ and -H₄ therapeutic approaches. Moreover, research is beginning to shed light on a role of H₄- receptors in mast cell precursor trafficking to various tissues commonly affected by allergic inflammation. Furthermore, H₄-receptors are also expressed on mature basophils and other effector cells of allergic reactions, such as eosinophils. This presents exciting possibilities in terms of potentially modulating the proallergic function of these cells as well as preventing the effects of histamine on target organs and cells.