Multiple sclerosis (MS) is caused by immune-mediated damage of myelin sheath. Current
therapies aim to block such immune responses. However, this blocking is not sufficiently specific and hence compromises immunity, leading to severe side effects. In addition, blocking medications usually provide transient effects and require frequent administration, which further increases the chance to compromise immunity. In this regard, myelin-specific
therapy may provide the desired specificity and a long-lasting
therapeutic effect by inducing myelin-specific regulatory T (Treg) cells. Tolerogenic dendritic cells (TolDCs) are one such
therapy. However, ex vivo generated TolDCs may be converted into immunogenic DCs in a proinflammatory environment. In this study, we identified a potential novel myelin-specific
therapy that works with immunogenic DCs, hence without the in vivo conversion concern. We showed that immunization with DCs, engineered to overexpress
25-hydroxyvitamin D 1α-hydroxylase for de novo synthesis of a focally high
1,25-dihydroxyvitamin D concentration in the peripheral lymphoid tissues, induced Treg cells. In addition, such engineered DCs, when pulsed with a myelin
antigen, led to myelin-specific suppression of ongoing
experimental allergic encephalomyelitis (an MS animal model), and the disease suppression depended on
forkhead-box-protein-P3(foxp3)+ Treg cells. Our data support a novel concept that immunogenic DCs can be engineered for myelin-specific
therapy for MS.-Li, C.-H., Zhang, J., Baylink, D. J., Wang, X., Goparaju, N. B., Xu, Y., Wasnik, S., Cheng, Y., Berumen, E. C., Qin, X., Lau, K.-H. W., Tang, X. Dendritic cells, engineered to overexpress
25-hydroxyvitamin D 1α-hydroxylase and pulsed with a myelin
antigen, provide myelin-specific suppression of ongoing
experimental allergic encephalomyelitis.