Regulation of cutaneous immunity by the environment: An important role for UV irradiation and vitamin D

Cutaneous immunity can be controlled by environmental factors such as ultraviolet (UV) irradiation. UV irradiation affects keratinocytes, antigen presenting cells, such as epidermal Langerhans cells (LC), and T lymphocytes. LC are specialized in antigen presentation. Upon encountering exogenous antigens they migrate to skin draining lymph nodes where they present skin-acquired antigens to naive T cells resulting in effector T cell differentiation. T cell effector functions depend on the activation state of LC, which can be influenced by UV irradiation. After completion T cell mediated cutaneous immune responses need to be downregulated. In this context, CD4(+)CD25(+) regulatory T cells have been shown to play an important role in the suppression of cellular immune responses via inhibition of T cell proliferation. Naturally occurring regulatory T cells develop in the thymus and on the molecular level members of the B7- and TNF-superfamilies are critically involved in the peripheral maintenance of CD4(+)CD25(+) T cells. Substantial evidence exists that peripheral regulatory T cells are responsive to environmental stimuli including UV irradiation. UV-induced regulatory T cells are expanded by UV-exposed cutaneous LC and recently, epidermal expression of vitamin D3 or RANKL (CD254) has been shown to connect the environment to the immune system via expansion of CD4(+)CD25(+) regulatory T cells. (C) 2009 Elsevier B.V. All rights reserved.