Peptide-MHC-Based Nanomedicines for the Treatment of Autoimmunity: Engineering, Mechanisms, and Diseases

被引:18
作者
Serra, Pau [1 ]
Santamaria, Pere [1 ,2 ,3 ,4 ]
机构
[1] Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain
[2] Univ Calgary, Julia McFarlane Diabet Res Ctr JMDRC, Calgary, AB, Canada
[3] Univ Calgary, Dept Microbiol Immunol & Infect Dis, Snyder Inst Chron Dis, Calgary, AB, Canada
[4] Univ Calgary, Hotchkiss Brain Inst, Cumming Sch Med, Calgary, AB, Canada
来源
FRONTIERS IN IMMUNOLOGY | 2021年 / 11卷
基金
加拿大健康研究院;
关键词
peptide-major histocompatibility complex molecules; nanoparticles; autoimmune diseases; T-cell re-programming; T-regulatory type 1 cells;
D O I
10.3389/fimmu.2020.621774
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The development of autoimmunity results from a breakdown of immunoregulation and involves cellularly complex immune responses against broad repertoires of epitope specificities. As a result, selective targeting of specific effector autoreactive T- or B-cells is not a realistic therapeutic option for most autoimmune diseases. Induction of autoantigen-specific regulatory T-cells capable of effecting bystander (dominant), yet tissue-specific, immunoregulation has thus emerged as a preferred therapeutic alternative. We have shown that peptide-major histocompatibility complex (pMHC)-based nanomedicines can re-program cognate autoantigen-experienced T-cells into disease-suppressing regulatory T-cells, which in turn elicit the formation of complex regulatory cell networks capable of comprehensively suppressing organ-specific autoimmunity without impairing normal immunity. Here, we summarize the various pMHC-based nanomedicines and disease models tested to date, the engineering principles underpinning the pharmacodynamic and therapeutic potency of these compounds, and the underlying mechanisms of action.
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页数:9
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