Cutaneous immunity can be controlled by environmental factors, like UV irradiation, which affects different cell types in the skin such as keratinocytes, epidermal Langerhans cells, and T cells. Langerhans cells, as specialized antigen presenting cells, encounter exogenous antigens, migrate to skin draining lymph nodes, and present skin-acquired antigens to naive T cells resulting in effector T cell differentiation. Effector T cell functions depend on the activation state of Langerhans cells, which can be modulated by UV irradiation in combination with co-stimulatory signals. Besides activating effector T cells, Langerhans cells from UV-irradiated skin have been shown to play a critical role in the peripheral expansion of immunosuppressive regulatory T cells. Notably, co-stimulatory signals via the receptor activator of NF-κB (RANK) and its ligand RANKL seem to connect environmental factors, such as UV irradiation to the immune system since blocking RANK-RANKL interactions abolishes the peripheral expansion of UV-induced regulatory T cells and accordingly, increases skin inflammation in mouse models of contact allergy or autoimmunity and upregulates spontaneous tumor development as well as tumor growth in a model of photocarcinogenesis.