Shikonin can enhance the efficiency of DNA vaccine via induction of Rantes and recruitment of dendritic cells
Shikonin, a chemically defined, potent immunosuppressive phytocompound isolated from Lithospermum erythrorhizon (Boraginaceae), has been shown to confer a variety of pharmacological activities, e.g., anti-inflammatory, wound-healing and anti-tumor activities. Dendritic cells (DCs) are dedicated antigen-presenting cells that play a major role not only in the initiation of T cell-mediated immunity but also in cross-talks between the innate and adaptive immunities. DCs act as sentinel cells, for uptake and processing of foreign antigens, they then traffic to the draining lymph nodes (LNs) through nonlymphoid peripheral tissues. There is accumulating evidence that the cell density and the cell differentiation and maturation status of skin DCs may greatly contribute to the efficiency of various gene-based strategies currently under development.
In this study, we investigate how the anti-inflammatory activities of shikonin are involved in the augmentation of various cellular and molecular functions of DCs, including the recruitment, maturation, and migration of DCs, therefore, shikonin could overcome some of the limitations of DNA vaccine and lead the improvement of the efficiency of DNA vaccine. Our study show that shikonin can suppress phenotypic and functional immature DCs maturation, subsequently alter their chemotactic response to CCL21, attenuate the migratory activity of matured DCs homing to lymphoid tissue and promote leukocytes recruitment by Rantes induction from keratinocytes.
To our knowledge, mechanistic and detailed molecular studies of shikonin or other phytocompounds on the enhancement of leukocytes recruitment to a specific targeted tissue have not been previously reported. Putting all finding together we hypothesized that shikonin can provide a microenvironment for sequestering immature DCs into a concentrated high cell-dose population in specific tissue and synchronize DCs into immature status, which in terms to create clinical opportunities for possible application of potential adjutants for DNA vaccine.