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 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, we review the expression and function of the H4 receptor with a focus on dermal and articular tissues. In skin, the H4 receptor is expressed in both the epidermis and dermis, with stronger receptor expression in the epidermis. In articular tissue, H4 receptor expression has been detected in synovial cells. Chondrocytes, a major cell sources for cartilage tissue engineering, also express the H4 receptor. Further understanding of the functions of H4 receptors in non-hematopoietic cells might lead to novel treatments for diseases with unmet needs.
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