Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N. Pine Street, Baltimore, MD 21201, United States.
Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 W. Baltimore Street, Baltimore, MD 21201, United States.
Adv Drug Deliv Rev. 2023 Dec;203:115141. doi: 10.1016/j.addr.2023.115141. Epub 2023 Nov 18.
The prevalence of immune-mediated disorders, including autoimmune conditions and allergies, is steadily increasing. However, current therapeutic approaches are often non-specific and do not address the underlying pathogenic condition, often resulting in impaired immunity and a state of generalized immunosuppression. The emergence of technologies capable of selectively inhibiting aberrant immune activation in a targeted, antigen (Ag)-specific manner by exploiting the body's intrinsic tolerance pathways, all without inducing adverse side effects, holds significant promise to enhance patient outcomes. In this review, we will describe the body's natural mechanisms of central and peripheral tolerance as well as innovative delivery strategies using cells and biomaterials targeting innate and adaptive immune cells to promote Ag-specific immune tolerance. Additionally, we will discuss the challenges and future opportunities that warrant consideration as we navigate the path toward clinical implementation of tolerogenic strategies to treat immune-mediated diseases.
免疫介导性疾病(包括自身免疫性疾病和过敏)的患病率正在稳步上升。然而,目前的治疗方法往往缺乏特异性,无法解决潜在的致病情况,常常导致免疫受损和全身性免疫抑制状态。出现了一些技术,这些技术能够通过利用机体内在的耐受途径,以靶向、抗原(Ag)特异性的方式选择性地抑制异常的免疫激活,而不会引起不良反应,这为改善患者预后带来了巨大的希望。在这篇综述中,我们将描述机体中枢和外周耐受的天然机制,以及利用细胞和生物材料靶向固有和适应性免疫细胞以促进 Ag 特异性免疫耐受的创新传递策略。此外,我们还将讨论在我们朝着将耐受策略临床应用于治疗免疫介导性疾病的方向前进时,需要考虑的挑战和未来机遇。