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载有雷帕霉素和自身抗原的聚合物纳米粒诱导抗原特异性免疫耐受,预防小鼠白癜风。

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

机构信息

Department of Dermatology, Weifang Yidu Central Hospital, Qingzhou, Shandong, China.

Department of Rheumatology, Weifang Yidu Central Hospital, Qingzhou, Shandong, China.

出版信息

Hum Vaccin Immunother. 2021 Jul 3;17(7):1923-1929. doi: 10.1080/21645515.2021.1872342. Epub 2021 Feb 22.

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 (NP) and investigated their effects on vitiligo. We treated bone marrow-derived dendritic cells (BMDCs) from TrpHEL mice with NP and monitored the phenotype of BMDCs. We investigated the effects of NP-treated BMDCs on CD4 T cell proliferation and differentiation. We administrated NP to TCR-TrpHEL mice and investigated the effects on vitiligo. We found that BMDCs can uptake the NP, which resulted in decreased expression of costimulation molecules CD80 and CD86 in BMDCs. BMDCs treated with NP suppressed antigen-specific CD4 T cell proliferation while promoted the differentiation of these CD4 T cell to Tregs . Administration of NP 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.

摘要

白癜风是一种自身免疫性疾病,其特征是皮肤斑块失去色素。CD4 T 细胞被认为与白癜风有关,而调节性 T 细胞(Tregs)可能改善白癜风。雷帕霉素与自身抗原一起已被证明可诱导免疫耐受并促进多种自身免疫性疾病中的 Tregs。在本研究中,我们合成了含有雷帕霉素和自身抗原 HEL(NP)的纳米颗粒,并研究了它们对白癜风的影响。我们用 NP 处理来自 TrpHEL 小鼠的骨髓来源树突状细胞(BMDCs),并监测 BMDCs 的表型。我们研究了 NP 处理的 BMDCs 对 CD4 T 细胞增殖和分化的影响。我们将 NP 给予 TCR-TrpHEL 小鼠,并研究了对白癜风的影响。我们发现 BMDCs 可以摄取 NP,这导致 BMDCs 中共刺激分子 CD80 和 CD86 的表达降低。NP 处理的 BMDCs 抑制抗原特异性 CD4 T 细胞增殖,同时促进这些 CD4 T 细胞向 Tregs 分化。给予 NP 给 TCR-TrpHEL 小鼠可改善白癜风,促进 Treg 产生,并抑制 IFN-γ和 IL-6 的产生,同时诱导 IL-10 的产生。因此,我们的研究提供了实验证据,表明含有雷帕霉素和自身抗原的纳米颗粒可诱导抗原特异性免疫耐受并预防白癜风。

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J Investig Dermatol Symp Proc. 2017 Oct;18(2):S38-S45. doi: 10.1016/j.jisp.2016.10.023.
3
Vitiligo: Mechanistic insights lead to novel treatments.白癜风:机制研究新进展带来新疗法
J Allergy Clin Immunol. 2017 Sep;140(3):654-662. doi: 10.1016/j.jaci.2017.07.011. Epub 2017 Aug 1.
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