Vitamin D augments house dust mite-mediated Th2 responses in human pulmonary dendritic cells (HYP6P.267)

Low serum levels of vitamin D (VD3) have been implicated in multiple immune disorders including atopic asthma. Other studies have shown that VD3 promotes monocyte-derived dendritic cell (MDDC) differentiation into tolerogenic DCs, which in turn induce regulatory T cells. However, we have found that VD3 actually augments allergen-induced Th2 cytokines. Specifically, cells isolated from human lung draining lymph nodes produced more IL-13 when treated with a combination of VD3 and the common allergen house dust mite (HDM) than either treatment alone. Similarly, when peripheral blood-derived MDDCs were co-treated with VD3 and HDM, these cells were able to induce less IFNγ, but more IL-4, from allogeneic CD4 T cells in a mixed lymphocyte reaction. In both MDDCs and pulmonary DCs, co-treatment with VitD and HDM led to a phenotype distinct from either treatment alone, as the DCs expressed both the stimulatory molecules HLA-DR and CD86 as well as the VD3-induced molecule thrombomodulin (CD141). Additionally, while the inhibitory receptors ILT3 and ILT4 are induced in MDDCs by VD3, we found that HDM was able to block this induction. Interestingly, the ILT4 ligand HLA-G was increased in this population. Future studies will explore the role of DC-expressed HLA-G and its receptors on DC function. Together, these data indicate that while VD3 may induce markers of tolerance, common allergens abrogate this response in DCs to augment the induction of a Th2 response.