Polymeric nanoparticles containing rapamycin and autoantigen induce antigen-specific immunological tolerance for preventing vitiligo in mice

Abstract

Vitiligo is an autoimmune disease in which pigment is lost in patches of the skin. CD4⁺ T cells are implicated in vitiligo while regulatory T cells (Tregs) could ameliorate vitiligo. Rapamycin together with autoantigen have been shown to induce immunological tolerance and promote Tregs in multiple autoimmune diseases. In the current study, we synthesized nanoparticles containing rapamycin and autoantigen HEL_46-61 (NP_{HEL46-61/Rapa}) and investigated their effects on vitiligo. We treated bone marrow-derived dendritic cells (BMDCs) from TrpHEL mice with NP_{HEL46-61/Rapa} and monitored the phenotype of BMDCs. We investigated the effects of NP_{HEL46-61/Rapa}-treated BMDCs on CD4⁺ T cell proliferation and differentiation. We administrated NP_{HEL46-61/Rapa} to TCR-TrpHEL mice and investigated the effects on vitiligo. We found that BMDCs can uptake the NP_{HEL46-61/Rapa}, which resulted in decreased expression of costimulation molecules CD80 and CD86 in BMDCs. BMDCs treated with NP_{HEL46-61/Rapa} suppressed antigen-specific CD4⁺ T cell proliferation while promoted the differentiation of these CD4⁺ T cell to Tregs <i>in vitro</i>. Administration of NP_{HEL46-61/Rapa} to TCR-TrpHEL mice ameliorated vitiligo, promoted Treg production, and suppressed IFN-γ and IL-6 production, while induced IL-10 production. Therefore, our study provides experimental evidence that nanoparticles containing rapamycin and autoantigen could induce antigen-specific immunological tolerance and prevent vitiligo.