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.

There is debate as to whether vitamin D deficiency contributes towards the extent of the asthma epidemic. In this study, using a mouse model, we determined whether vitamin D deficiency in utero and during early life modulated the severity of asthma. Using dietary restriction, vitamin D(3) -replete and vitamin D(3) -deficient colonies of BALB/c mice were established. Utilizing the allergic airway disease model of asthma with the experimental allergen ovalbumin (OVA), we examined asthma-like responses 24 h after airway challenge with OVA in adult offspring born to vitamin D(3) -replete and vitamin D(3) -deficient mothers. The ability of airway-draining lymph node cells to proliferate and secrete cytokines in response to OVA ex vivo was significantly enhanced by vitamin D(3) deficiency. However, other aspects of allergic disease, including the numbers and proportions of inflammatory cells and cytokines in the lungs and the quantity of OVA-specific IgE in serum, were not modified. These results suggest that vitamin D(3) deficiency modulates the capacity of lymphocytes to respond to allergens.

Summary The severity of allergic diseases may be modified by vitamin D. However, the immune pathways modulated by the active form of vitamin D, 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3], are yet to be fully elucidated. In this study, naturally occurring CD4+ CD25+ cells from the skin‐draining lymph nodes (SDLN) of mice treated with topical 1,25(OH)2D3 had an increased ability to suppress T helper type 2 (Th2) ‐skewed immune responses. CD4+ CD25+ cells transferred from mice treated with topical 1,25(OH)2D3 into ovalbumin (OVA) ‐sensitized mice challenged intranasally with OVA 18 hr later, significantly suppressed the capacity of airway‐draining lymph node (ADLN) cells to proliferate and secrete cytokines in response to further OVA stimulation ex vivo. The CD4+ CD25+ cells from 1,25(OH)2D3‐treated mice also reduced airway hyperresponsiveness and the proportions of neutrophils and eosinophils in bronchoalveolar lavage fluid (BALF). To test the effect of 1,25(OH)2D3 on cells able to respond to a specific antigen, CD4+ CD25+ cells were purified from the SDLN of OVA‐T‐cell receptor (TCR) transgenic mice treated 4 days earlier with topical 1,25(OH)2D3. CD4+ CD25+ cells from OVA‐TCR mice treated with 1,25(OH)2D3 were able to alter BALF cell content and suppress ADLN responses to a similar degree to those cells from non‐transgenic mice, suggesting that the effect of 1,25(OH)2D3 was not related to TCR signalling. In summary, topical 1,25(OH)2D3 increased the regulatory capacity of CD4+ CD25+ cells from the SDLN to suppress Th2‐mediated allergic airway disease. This work highlights how local 1,25(OH)2D3 production by lung epithelial cells may modulate the suppressive activity of local regulatory T cells.