Humans obtain most of their vitamin D through the exposure of skin to sunlight. The immunoregulatory properties of vitamin D have been demonstrated in studies showing that vitamin D deficiency is associated with poor immune function and increased disease susceptibility. The benefits of moderate ultraviolet (UV) radiation exposure and the positive latitude gradients observed for some immune-mediated diseases may therefore reflect the activities of UV-induced vitamin D. Alternatively, other mediators that are induced by UV radiation may be more important for UV-mediated immunomodulation. Here, we compare and contrast the effects of UV radiation and vitamin D on immune function in immunopathological diseases, such as psoriasis, multiple sclerosis and asthma, and during infection.

Vitamin D deficiency causes deficits in lung function that are primarily explained by differences in lung volume. This study is the first to provide direct mechanistic evidence linking vitamin D deficiency and lung development, which may explain the association between obstructive lung disease and vitamin D status.

The immunomodulatory effects of vitamin D have been described following chronic oral administration to mice or supplementation of cell cultures with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D. In this study, topically applied 1,25(OH)2D3, enhanced the suppressive capacity of CD4+CD25+ cells from the draining lymph nodes. The effects of topical 1,25(OH)2D3 were compared with those of UVB irradiation, which is the environmental factor required for 1,25(OH)2D3 production in skin. CD4+ cells from the skin-draining lymph nodes (SDLN) of either 1,25(OH)2D3-treated or UVB-irradiated mice had reduced capacity to proliferate to Ags presented in vitro, and could suppress Ag-specific immune responses upon adoptive transfer into naive mice. This regulation was lost upon removal of CD4+CD25+ cells. Furthermore, purified CD4+CD25+ cells from the SDLN of 1,25(OH)2D3-treated or UVB-irradiated mice compared with equal numbers of CD4+CD25+ cells from control mice had increased capacity to suppress immune responses in both in vitro and in vivo assay systems. Following the sensitization of recipient mice with OVA, the proportion of CD4+Foxp3+ cells of donor origin significantly increased in recipients of CD4+CD25+ cells from the SDLN of 1,25(OH)2D3-treated mice, indicating that these regulatory T cells can expand in vivo with antigenic stimulation. These studies suggest that 1,25(OH)2D3 may be an important mediator by which UVB-irradiation exerts some of its immunomodulatory effects.

The role of vitamin D in curtailing the development of obesity and comorbidities such as the metabolic syndrome (MetS) and type 2 diabetes has received much attention recently. However, clinical trials have failed to conclusively demonstrate the benefits of vitamin D supplementation. In most studies, serum 25-hydroxyvitamin D [25(OH)D] decreases with increasing BMI above normal weight. These low 25(OH)D levels may also be a proxy for reduced exposure to sunlight-derived ultraviolet radiation (UVR). Here we investigate whether UVR and/or vitamin D supplementation modifies the development of obesity and type 2 diabetes in a murine model of obesity. Long-term suberythemal and erythemal UVR significantly suppressed weight gain, glucose intolerance, insulin resistance, nonalcoholic fatty liver disease measures; and serum levels of fasting insulin, glucose, and cholesterol in C57BL/6 male mice fed a high-fat diet. However, many of the benefits of UVR were not reproduced by vitamin D supplementation. In further mechanistic studies, skin induction of the UVR-induced mediator nitric oxide (NO) reproduced many of the effects of UVR. These studies suggest that UVR (sunlight exposure) may be an effective means of suppressing the development of obesity and MetS, through mechanisms that are independent of vitamin D but dependent on other UVR-induced mediators such as NO.Obesity has significant effects on our health and wellbeing: obese people have increased comorbidities resulting from cardiovascular disease, type 2 diabetes, breast and colon cancers, dementia, and depression. Vitamin D deficiency is recognized as a health problem affecting many individuals worldwide (1) and may contribute to the development of obesity. Insufficient levels of vitamin D are associated with obesity, and obese people are more likely than others to be vitamin D deficient (reviewed in Earthman et al.

Pregnancy is a time of vulnerability for vitamin D insufficiency, and there is an emerging literature associating low levels of 25(OH)-vitamin D with depressive symptoms. However, the link between 25(OH)-vitamin D status in pregnancy and altered risk of postnatal depressive symptoms has not been examined. We hypothesise that low levels of 25(OH)-vitamin D in maternal serum during pregnancy will be associated with a higher incidence of postpartum depressive symptoms. We prospectively collected sera at 18 weeks gestation from 796 pregnant women in Perth (1989-1992) who were enrolled in the Western Australian Pregnancy Cohort (Raine) Study and measured levels of 25(OH)-vitamin D. Women reported postnatal depressive symptoms at 3 days post-delivery. Women in the lowest quartile for 25(OH)-vitamin D status were more likely to report a higher level of postnatal depression symptoms than women who were in the highest quartile for vitamin D, even after accounting for a range of confounding variables including season of birth, body mass index and sociodemographic factors. Low vitamin D during pregnancy is a risk factor for the development of postpartum depression symptoms.

Aims/hypothesis Exposure to sunlight has the potential to suppress metabolic dysfunction and obesity. We previously demonstrated that regular exposure to low-doses of ultraviolet radiation (UVR) reduced weight gain and signs of diabetes in male mice fed a high-fat diet, in part via release of nitric oxide from skin. Here, we explore further mechanistic pathways through which lowdose UVR exerts these beneficial effects. Methods We fed mice with a luciferase-tagged Ucp1 gene (which encodes uncoupling protein-1 [UCP-1]), referred to here as the Ucp1 luciferase transgenic mouse ('Thermomouse') a high-fat diet and examined the effects of repeated exposure to low-dose UVR on weight gain and development of metabolic dysfunction as well as UCP-1-dependent thermogenesis in interscapular brown adipose tissue (iBAT). Results Repeated exposure to low-dose UVR suppressed the development of glucose intolerance and hepatic lipid accumulation via dermal release of nitric oxide while also reducing circulating IL-6 (compared with mice fed a high-fat diet only). Dietary nitrate supplementation did not mimic the effects of low-dose UVR. A single low dose of UVR increased UCP-1 expression (by more than twofold) in iBAT of mice fed a low-fat diet, 24 h after exposure. However, in mice fed a high-fat diet, there was no effect of UVR on UCP-1 expression in iBAT (compared with mock-treated mice) when measured at regular intervals over 12 weeks. More extensive circadian studies did not identify any substantial shifts in UCP-1 expression in mice exposed to low-dose UVR, although skin temperature at the interscapular site was reduced in UVR-exposed mice. The appearance of cells with a white adipocyte phenotype ('whitening') in iBAT induced by consuming the high-fat diet was suppressed by exposure to low-dose UVR in a nitric oxide-dependent fashion. Significant shifts in the expression of important core gene regulators of BAT function Gursimran K. Dhamrait and Kunjal Panchal contributed equally to this study.

UVB irradiation of skin suppresses AHR and cellular responses of the airways to respiratory allergens. Further, this study implicates UVB or its downstream mediators as a potential approach to reducing the severity of asthma.

Direct UV irradiation of dendritic cells and Langerhans cells reduces their Ag presenting ability. However, the effects of UV on CD11c+ cells located distally to the point of irradiation are poorly understood. Three days after UV irradiation (8 kJ/m2) of BALB/c mice, bone marrow cells were isolated and cultured for 7 d with IL-4 and GM-CSF for the propagation of CD11c+ cells. Bone marrow-derived CD11c+ cells from UV-irradiated or nonirradiated mice were loaded with dinitrobenzene sulfonic acid and injected into the ear pinnas of naive BALB/c mice. After 7 d, the ears were painted with 2,4-dinitro-1-fluorobenzene and the ear swelling determined 24 h later. A reduced contact hypersensitivity response was found in mice injected with CD11c+ cells from the UV-irradiated animals compared with those injected with cells from the nonirradiated animals. Further, a long-lasting suppression of the memory response to 2,4-dinitro-1-fluorobenzene was created. This suppressed response corresponded to increased IL-10 and PGE2 secretion by freshly isolated bone marrow cells from UV-irradiated mice, and to increased myelopoiesis. The reduction in competence of bone marrow-derived CD11c+ cells from UV-irradiated mice was not due to delayed maturation, as it was maintained upon LPS exposure prior to CD11c+ cell purification. The UV-induced effect was reversed by the administration of indomethacin to mice prior to UV irradiation and could be reproduced by s.c. PGE2. These results show that UV irradiation of mice can affect the function of bone marrow-derived CD11c+ cells via a mechanism inhibitable by indomethacin; this pathway is likely to contribute to systemic UV-induced immunosuppression.