1,25‐dihydroxyvitamin D3 enhances the ability of transferred CD4+ CD25+ cells to modulate T helper type 2‐driven asthmatic responses

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.