[Expression and function of the histamine receptors in dermal and articular tissues]

Histamine was first identified in 1910 as a physiologically active amine. It is now recognized for its multiple regulatory activities in the digestive, neuronal, and immune systems, and new roles are still being elucidated. Histamine exerts its effects through four distinct receptor subtypes. The histamine H4 receptor was identified in 2000 and is the most recently identified of the four histamine receptors. It is expressed primarily in immune cells and is involved in physiologic functions related to inflammation and allergy. Recently, the H4 receptor was highlighted as a promising therapeutic target in atopic dermatitis, asthma, and chronic arthritis. In fact, some H4 receptor antagonists have reached clinical trials for the treatment of asthma, atopic dermatitis, and allergic rhinitis. Based on an initial assessment of its distribution, the H4 receptor has been referred to as the histamine receptor of the hematopoietic system. However, the H4 receptor has also been implicated in the regulation of other non-hematopoietic systems. Here, I review the expression and function of the identified histamine receptors, including the H4 receptor with a focus on articular and dermal tissues. In articular tissue, H4 receptor expression has been detected in synovial cells. Chondrocytes, a major cell source for cartilage tissue engineering, also express the H4 receptor. In skin, the H4 receptor is expressed in both the epidermis and dermis, with stronger receptor expression in the epidermis. Further understanding of the functions of H4 receptors in non-hematopoietic cells might lead to novel treatments for diseases with unmet medical needs.