A critical role for dermal mast cells in cis-urocanic acid-induced systemic suppression of contact hypersensitivity responses in mice

Many studies have implicated cis-urocanic acid (cis-UCA) in UVB-induced imm unomodulation, The strongest evidence came from studies in mice whereby a c is-UCA antibody blocked UVB-induced suppression of delayed-type hypersensit ivity responses. Furthermore, in several studies, the cis-UCA antibody at l east partially reversed UVB suppression of contact hypersensitivity respons es. Previous reports suggested that cis-UCA was immunomodulatory through it s effects on keratinocytes, Langerhans cells, fibroblasts, T lymphocytes, n atural killer cells and monocytes/macrophages. As dermal mast cells were re cently demonstrated to be critical to UVB-induced systemic suppression of c ertain delayed-type and contact hypersensitivity responses, we investigated whether they were involved in the processes by which cis-UCA was immunomod ulatory, Not only was there a correlation between dermal mast cell prevalen ce and the degree of susceptibility of different strains of mice to the imm unomodulatory effects of cis-UCA, there was also a functional link. Mast ce ll-depleted W-f/W-f mice were rendered susceptible to immunomodulation by c is-UCA injected subcutaneously only after their dorsal skin had been recons tituted with bone marrow-derived mast cell precursors. These studies sugges t that mast cells are critical to the processes by which cis-UCA suppresses systemic contact hypersensitivity responses to the hapten, trinitrochlorob enzene, in mice.