UVB-dependent modulation of epidermal cytokine network: roles in UVB-induced depletion of Langerhans cells and dendritic epidermal T cells.

The epidermis of mice consists of three cellular components, i.e., keratinocytes, Langerhans cells (LC), and dendritic epidermal T cells (DETC). Each epidermal subpopulation produces a different set of cytokines, thereby forming a unique cytokine milieu. These cytokines, in turn, support the survival and growth of LC and DETC and regulate their immunological functions. LC and DETC play important, but distinct, effector roles in protective immunity against antigens that are generated in or penetrate into the epidermis. Acute or chronic exposure of mice to ultraviolet B (UVB) radiation is known to impair this cutaneous immunity, as evidenced by the failure to induce T cell-mediated immune reactions, by the generation of antigen-specific immunological unresponsiveness, and by the development of skin cancers. Importantly, these changes are associated with reduced densities of LC and DETC in UVB-exposed skin, suggesting that the deficiency in these epidermal leukocytes may account for some of the deleterious influences of UVB radiation on skin. Here I will review the recent advance in our understanding of the mechanisms by which UVB radiation may deplete LC and DETC from epidermis. More specifically, I will discuss the following possibilities: a) UVB-mediated suppression of the production of relevant growth factors for LC and DETC, b) UVB-induced abrogation of surface expression of growth factor receptors, and c) UVB-triggered apoptotic cell death in epidermal leukocytes.