Polymeric nanoparticles containing rapamycin and autoantigen induce antigen-specific immunological tolerance for preventing vitiligo in mice
| Autor: | Mao Lin, Cai-Xia Tu, Xia Zhang, Baoxiang Zhang, Minghong He, Daji Liu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
T cell
030231 tropical medicine Immunology Vitiligo Autoantigens 03 medical and health sciences Mice 0302 clinical medicine Antigen specific medicine Immunology and Allergy Animals 030212 general & internal medicine Pharmacology Autoimmune disease CD86 Sirolimus integumentary system Chemistry Dendritic Cells medicine.disease Phenotype In vitro medicine.anatomical_structure Cancer research Nanoparticles CD80 Research Paper |
| Zdroj: | Hum Vaccin Immunother |
| ISSN: | 2164-554X |
| Popis: | 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 in vitro. 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. |
| Databáze: | OpenAIRE |
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