Acute Erythemal Ultraviolet Radiation Causes Systemic Immunosuppression in the Absence of Increased 25-Hydroxyvitamin D3 Levels in Male Mice

Vitamin D is synthesised by ultraviolet (UV) irradiation of skin and is hypothesized to be a direct mediator of the immunosuppression that occurs following UV radiation (UVR) exposure. Both UVR and vitamin D drive immune responses towards tolerance by ultimately increasing the suppressive activities of regulatory T cells. To examine a role for UVR-induced vitamin D, vitamin D-3-deficient mice were established by dietary vitamin D-3 restriction. In comparison to vitamin D-3-replete mice, vitamin D-3-deficient mice had significantly reduced serum levels of 25-hydroxyvitamin D-3 (25(OH)D-3, < 20 nmol.L-1) and 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3, < 20 pmol.L-1). Following either acute erythemal UVR, or chronic sub-erythemal UVR (8 exposures over 4 weeks) treatment, serum 25(OH)D-3 levels significantly increased in vitamin D-3-deficient female but not male mice. To determine if UVR-induced vitamin D was a mediator of UVR-induced systemic immunosuppression, responses were measured in mice that were able (female) or unable (male) to increase systemic levels of 25(OH)D-3 after UVR. Erythemal UVR (>= 4 kJ/m(2)) suppressed contact hypersensitivity responses (T helper type-1 or -17), aspects of allergic airway disease (T helper type-2) and also the in vivo priming capacity of bone marrow-derived dendritic cells to a similar degree in female and male vitamin D-3-deficient mice. Thus, in male mice, UVR-induced 25(OH)D-3 is not essential for mediating the immunosuppressive effects of erythemal UVR.