Histamine suppresses T helper 17 responses mediated by transforming growth factor-β1 in murine chronic allergic contact dermatitis

Abstract

Allergic skin diseases are caused by the introduction of antigen into the skin. Repeated application of antigens prompts the development of atopic dermatitis (AD) and chronic allergic contact dermatitis (CACD). Histamine facilitates the development of chronic lesions in CACD. T helper (Th)17 cells are less prevalent in the chronic lesional skin compared to acute lesional skin in AD and CACD. The present experiment determined the effects of histamine in regulating Th17 in a murine model of CACD. CACD was induced by repeated epicutaneous challenge of 2,4,6-trinitro-1-chlorobenzene in histidine decarboxylase (HDC) (-/-) mice. Th17 response were analyzed by transforming growth factor (TGF)-β1, interleukin (IL)-17 and IL-22 levels in lesional skin. TGF-β1 was injected into the dermis of CACD-developing mice. Histamine H1 or H4 receptor antagonist were orally administrated in CACD-developing mice. IL-17 and IL-22 levels were lower in HDC (+/+) mice compared to HDC (-/-) mice. TGF-β1 levels were also lower in HDC (+/+) mice compared to HDC (-/-) mice. TGF-β1 injection increased IL-17 and IL-22 levels in the lesional skin of HDC (+/+) mice. Histamine H1 or H4 receptor antagonist administration also increased TGF-β1, IL-17 and IL-22 levels in the lesional skin of HDC (+/+) mice. In conclusion, histamine suppresses Th17 function in murine CACD. This effect was induced by the down-regulation of TGF-β1 through histamine H1 and H4 receptors.