All‐trans retinoic acid induces functional maturation of epidermal Langerhans cells and protects their accessory function from ultraviolet radiation

Abstract

Retinoids provide some protection against ultraviolet radiation-induced skin damage. We have previously shown that topical all-trans retinoic acid prevents ultraviolet light from reducing the density of epidermal Langerhans cells in the epidermis but does not inhibit the development of immunosuppression to a locally applied contact sensitizer. We therefore investigated the ability of all-trans retinoic acid to modulate Langerhans cell induction of allogeneic T-cell proliferation in the mixed epidermal cell lymphocyte reaction. Langerhans cells isolated from all-trans retinoic acid-treated mice induced an enhanced mixed epidermal cell lymphocyte reaction. This is similar to Langerhans cells cultured with granulocyte-macrophage colony stimulating factor. Retinoic acid treatment also enhanced the allogeneic cell-stimulating capability of Langerhans cells isolated from ultraviolet-irradiated mice. Langerhans cells from all-trans retinoic acid-treated, ultraviolet-irradiated mice which were "matured" by 3 days in culture induced a larger mixed epidermal cell lymphocyte reaction than mice treated with solvent and ultraviolet irradiation. Thus all-trans retinoic acid treatment of mice causes Langerhans cell maturation and inhibits ultraviolet light from reducing their density or impairing their allogeneic cell-stimulating capacity. However, these mice remained immunosuppressed upon application of a contact sensitizer to irradiated or unirradiated skin. It is thus likely that, whereas all-trans retinoic acid protects local Langerhans cell numbers and function, it does not inhibit the production of an ultraviolet radiation-induced photoproduct which causes immunosuppression.

Topical All-trans Retinoic Acid Augments Ultraviolet Radiation-Induced Increases in Activated Melanocyte Numbers in Mice

“…In mammals, vitamin A activity is fulfilled by three major compounds: retinol, retinal, and retinoic acid (RA; vitamin A acid); and perhaps by a number of their metabolites. RA has been found to modulate many of the effects of UVR on the skin, including clinical and histologic improvement of photodamaged skin (Gilchrest, 1992;Griffiths et al, 1993a), and protection from UVR-induced reduction of Langerhans cell numbers (Ho et al, 1991), and function (Dunlop et al, 1994).…”

Real-TimeReflectance Confocal Microscopy, a Noninvasive Tool for in vivo Quantitative Evaluation of Comedolysis in the Rhino Mouse Model

“…Retinoids may have induced changes in the activity of specific cells or altered the cell's scattering properties resulting in increased brightness. However, there are reports describing the immunomodulatory effects of the topical application of retinoids on Langerhans cells, dendritic immune cells present in the skin [26,27] . In our study, immunohistochemistry for Langerhans cells was performed in vertical sections of biopsy tissues, making difficult a visual (qualitative) comparison with the horizontal confocal sections, and the number of positive cells per field of view was too low for an accurate statistical analysis.…”