A Critical Role for Dermal Mast Cells in Cis ‐Urocanic Acid‐induced Systemic Suppression of Contact Hypersensitivity Responses in Mice

Many studies have implicated cu‐urocanic acid (cu‐UCA) in UVB‐induced immunomodulation. The strongest evidence came from studies in mice whereby a cis‐ UCA antibody blocked UVB‐induced suppression of de‐layed‐type hypersensitivity responses. Furthermore, in several studies, the cis ‐UCA antibody at least partially reversed UVB suppression of contact hypersensitivity responses. Previous reports suggested that cis ‐UCA was immunomodulatory through its effects on keratinocytes, Langerhans cells, fibroblasts, T lymphocytes, natural killer cells and monocytes/macrophages. As dermal mast cells were recently demonstrated to be critical to UVB‐induced systemic suppression of certain delayed‐type and contact hypersensitivity responses, we investigated whether they were involved in the processes by which cu‐UCA was immunomodulatory. Not only was there a correlation between dermal mast cell prevalence and the degree of susceptibility of different strains of mice to the immunomodulatory effects of cis ‐UCA, there was also a functional link. Mast cell‐depleted W f /W f mice were rendered susceptible to immunomodulation by cis ‐UCA injected subcutaneously only after their dorsal skin had been reconstituted with bone marrow‐derived mast cell precursors. These studies suggest that mast cells are critical to the processes by which cis ‐UCA suppresses systemic contact hypersensitivity responses to the hapten, trinitrochlorobenzene, in mice.