Strategies to Use Nanoparticles to Generate CD4 and CD8 Regulatory T Cells for the Treatment of SLE and Other Autoimmune Diseases.
Strategies to Use Nanoparticles to Generate CD4 and CD8 Regulatory T Cells for the Treatment of SLE and Other Autoimmune Diseases.
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DOI：
10.3389/fimmu.2021.681062
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发表时间：
2021
影响因子：
7.3
通讯作者：
La Cava A
中科院分区：
文献类型：
--
作者：
Horwitz DA;Bickerton S;La Cava A
自身免疫性疾病是免疫调节的紊乱，其中负责自我耐受的机制被破坏，病理性T细胞克服了通常控制它们的T调节细胞（Tregs）的保护作用。其结果可能是引发慢性炎症性疾病。系统性红斑狼疮（SLE）和其他自身免疫性疾病通常用具有广泛抑制作用的药物或生物制剂治疗。这些药物可以阻止疾病进展，但很少治愈，同时有严重的不良副作用。最近，纳米颗粒已被设计用于纠正稳态调节缺陷和再生治疗性抗原特异性treg。一些方法使用纳米颗粒靶向抗原提呈细胞，将它们的支持从致病性T细胞转向保护性treg细胞。其他人则使用纳米颗粒直接靶向T细胞来诱导和扩增CD4+和CD8+ treg。其中一些靶向T细胞的纳米颗粒已被配制成作为耐受性人工抗原提呈细胞。本文讨论了这些不同的纳米颗粒制剂的性质和策略，使用它们在自身免疫性疾病的治疗。Treg对效应细胞的优势的恢复和维持应该促进自身免疫性疾病的长期缓解，并最终在易感个体中预防它们。
Autoimmune diseases are disorders of immune regulation where the mechanisms responsible for self-tolerance break down and pathologic T cells overcome the protective effects of T regulatory cells (Tregs) that normally control them. The result can be the initiation of chronic inflammatory diseases. Systemic lupus erythematosus (SLE) and other autoimmune diseases are generally treated with pharmacologic or biological agents that have broad suppressive effects. These agents can halt disease progression, yet rarely cure while carrying serious adverse side effects. Recently, nanoparticles have been engineered to correct homeostatic regulatory defects and regenerate therapeutic antigen-specific Tregs. Some approaches have used nanoparticles targeted to antigen presenting cells to switch their support from pathogenic T cells to protective Tregs. Others have used nanoparticles targeted directly to T cells for the induction and expansion of CD4+ and CD8+ Tregs. Some of these T cell targeted nanoparticles have been formulated to act as tolerogenic artificial antigen presenting cells. This article discusses the properties of these various nanoparticle formulations and the strategies to use them in the treatment of autoimmune diseases. The restoration and maintenance of Treg predominance over effector cells should promote long-term autoimmune disease remission and ultimately prevent them in susceptible individuals.
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