Actelated dextran microparticle delivery as a means to generate regulatory myeloid cells (IRC5P.470)

Myeloid cells (MC) have potent regulatory abilities but factors influencing the development of such regulatory myeloid cells (MC-regs) remain poorly understood. Retinoic acid (RA) is a metabolite of vitamin A that has regulatory abilities and impacts myeloid cell differentiation. We have previously shown that RA produces MC-regs that expressed increased IL-10, regulatory T (Treg) cells, and were able to suppress the proliferation and cytotoxicity of CD4+ and CD8+ T cells, respectively. We hypothesize that encapsulation of RA within acetalated dextran (AC-DEX) microparticles (MPs) can be used for targeted generation of MC-regs in vivo. We used MPs containing encapsulated FITC-labeled BSA to determine the relative uptake of Ac-DEX MPs by myeloid cell populations in vitro and in vivo. We found that labeled MPs were readily taken up by macrophages, DCs and myeloid progenitors in vitro. Following in vivo injection, increased percentage of FITC+ cells was seen in both CD11c+CD11b- and CD11c-CD11b+ cells in draining lymph nodes (DLN) over controls of free FITC or empty MP administration. When RA was encapsulated into MPs, CD11b+ cells within the DLNs had a increased PD-L1 expression and proliferation in DLNs was decreased. These results suggest that in vivo targeted delivery of regulatory compounds by Ac-DEX MPs can induce MC-regs which may be useful to treat inlammatory and immune-mediated diseases.