Background T regulatory cells (Tregs) provide beneficial effects in the suppression of autoimmune responses in systemic lupus erythematosus (SLE). We recently showed that poly(lactic-co-glycolic acid) PLGA nanoparticles (NPs) loaded with IL-2 and TGF-β could induce CD4+ and CD8+ Foxp3+ Tregs in vitro and in vivo, with resulting protective effects in mice that develop lupus-like disease following the transfer of donor T cells from DBA/2 mice into (C57BL/6 x DBA/2)F1 (BDF1) recipients.
Methods We produced NPs encapsulating IL-2 as acellular tolerogenic artificial antigen-presenting cell (aAPC)s for the induction of CD4+ and CD8+ Foxp3+ Tregs in vivo. aAPC NPs were also engineered to promote the tolerogenic activity of NK cells. Those acellular aAPCs were then tested for therapeutic efficacy in vivo in lupus-prone BDF1 mice.
Results The aAPC NPs induced CD4+ and CD8+ Tregs in vivo in BDF1 mice and protected the animals from lupus disease manifestations. At the NK cell level, protection from lupus-like disease could be ascribed to the production of TGF-β from the NP-induced NK cells. Finally, the use of aAPC NPs in humanized NSG mice expanded Tregs in numbers sufficient to protect mice from a rapidly evolving human anti-mouse graft-versus-host disease.
Conclusions These studies provide a proof-of-concept for the potential use of PLGA NPs as acellular aAPCs for the induction of therapeutically effective numbers of Tregs in conditions of pathologic deficit such as in SLE.
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