Effect of TCDD on the density of Langerhans cells in murine skin

Abstract

2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) is a prototype for a group of toxic polyhalogenated aromatic hydrocarbons. We have studied the effect of TCDD on skin, specifically the difference in cutaneous response of congenic haired (hr/+) and hairless ( hr hr mice. Topical application of 0.6 μg of TCDD induces epidermal hyperplasia/hyperkeratinization in the skin of hr hr mice, but does not affect the epidermis of congenic hr/+ littermates. Suppression of various parameters of the immune response has been found to be another effect of TCDD exposure in experimental animals. In the present study, we investigated the effect of topical treatment with TCDD on the density of epidermal immune cells, the Langerhans cells (LC), in the skin of hr hr and hr/+ mice. Results showed that TCDD-induced epidermal hyperplasia/hyperkeratinization in skin of hr hr mice is accompanied by an increase in the density of LC. In the skin of hr/+ mice, in which TCDD exposure does not induce hyperplastic changes, LC densities are not affected. The increase in LC densities in TCDD-treated hr hr mouse skin did not result in increased sensitivity of the skin to contact hypersensitization with dinitrofluorobenzene, as measured by changes in ear thickness. When hr hr murine skin was grafted into skin of hr/+ mice and the entire dorsal skin (including the graft) treated with TCDD, LC were increased in the grafted skin, but not in the surrounding hr/+ skin. Conversly, when hr/+ murine skin was grafted into hr hr mice and both treated with TCDD, there was no increase in the density of LC in the grafted hr/+ skin. Concomitant treatment of hairless mice with TCDD and with indomethacin did not affect the increase in the density of LC induced by TCDD treatment alone. These findings suggest that TCDD-induced epidermal changes in hr hr murine skin involve production of factors which mediate the increase in epidermal LC.