Flt3-L enhances trans-epithelial migration and antigen presentation of dendritic cells adoptively transferred to genital mucosa

Dendritic cells (DCs) play a critical role in shaping adaptive immunity. Systemic transfer of DCs by intravenous injection has been widely investigated to inform the development of immunogenic DCs for use as cellular therapies. Adoptive transfer of DCs to mucosal sites has been limited but serves as a valuable tool to understand the role of the microenvironment on mucosal DC activation, maturation and antigen presentation. Here, we show that chitosan facilitates transmigration of DCs across the vaginal epithelium in the mouse female reproductive tract (FRT). In addition, ex vivo programming of DCs with fms-related tyrosine kinase 3 ligand (Flt3-L) was found to enhance translocation of intravaginally administered DCs to draining lymph nodes (dLNs) and stimulate in vivo proliferation of both antigen-specific CD4+ and CD8+ T cells (cross-presentation). Mucosal priming with chitosan and DC programming may hold great promise to enhance efficacy of DC-based vaccination to the female genital mucosa.