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自身免疫性疾病的自身免疫机制演变和新的治疗策略。

Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders.

机构信息

Institute of Immunology, PLA, Third Military Medical University (Army Medical University), Chongqing, China.

Chongqing International Institute for Immunology, Chongqing, China.

出版信息

Signal Transduct Target Ther. 2024 Oct 4;9(1):263. doi: 10.1038/s41392-024-01952-8.


DOI:10.1038/s41392-024-01952-8
PMID:39362875
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11452214/
Abstract

Autoimmune disorders are characterized by aberrant T cell and B cell reactivity to the body's own components, resulting in tissue destruction and organ dysfunction. Autoimmune diseases affect a wide range of people in many parts of the world and have become one of the major concerns in public health. In recent years, there have been substantial progress in our understanding of the epidemiology, risk factors, pathogenesis and mechanisms of autoimmune diseases. Current approved therapeutic interventions for autoimmune diseases are mainly non-specific immunomodulators and may cause broad immunosuppression that leads to serious adverse effects. To overcome the limitations of immunosuppressive drugs in treating autoimmune diseases, precise and target-specific strategies are urgently needed. To date, significant advances have been made in our understanding of the mechanisms of immune tolerance, offering a new avenue for developing antigen-specific immunotherapies for autoimmune diseases. These antigen-specific approaches have shown great potential in various preclinical animal models and recently been evaluated in clinical trials. This review describes the common epidemiology, clinical manifestation and mechanisms of autoimmune diseases, with a focus on typical autoimmune diseases including multiple sclerosis, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, and sjögren's syndrome. We discuss the current therapeutics developed in this field, highlight the recent advances in the use of nanomaterials and mRNA vaccine techniques to induce antigen-specific immune tolerance.

摘要

自身免疫性疾病的特征是 T 细胞和 B 细胞对机体自身成分的异常反应,导致组织破坏和器官功能障碍。自身免疫性疾病影响世界许多地区的广泛人群,已成为公共卫生的主要关注点之一。近年来,我们对自身免疫性疾病的流行病学、危险因素、发病机制和机制有了实质性的了解。目前批准的自身免疫性疾病治疗方法主要是非特异性免疫调节剂,可能会导致广泛的免疫抑制,从而导致严重的不良反应。为了克服免疫抑制药物在治疗自身免疫性疾病方面的局限性,迫切需要精确和靶向特异性的策略。迄今为止,我们对免疫耐受机制的理解已经取得了重大进展,为开发针对自身免疫性疾病的抗原特异性免疫疗法提供了新途径。这些抗原特异性方法在各种临床前动物模型中显示出巨大的潜力,并在最近的临床试验中进行了评估。本文描述了自身免疫性疾病的常见流行病学、临床表现和发病机制,重点介绍了多发性硬化症、1 型糖尿病、类风湿性关节炎、系统性红斑狼疮和干燥综合征等典型自身免疫性疾病。我们讨论了该领域开发的当前疗法,强调了最近在利用纳米材料和 mRNA 疫苗技术诱导抗原特异性免疫耐受方面的进展。

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[9]
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[10]
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本文引用的文献

[1]
Efficacy and safety of sequential therapy with subcutaneous belimumab and one cycle of rituximab in patients with systemic lupus erythematosus: the phase 3, randomised, placebo-controlled BLISS-BELIEVE study.

Ann Rheum Dis. 2024-10-21

[2]
RNAi-based drug design: considerations and future directions.

Nat Rev Drug Discov. 2024-5

[3]
Effectiveness of autologous haematopoietic stem cell transplantation versus natalizumab in progressive multiple sclerosis.

J Neurol Neurosurg Psychiatry. 2024-7-15

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The present and future of bispecific antibodies for cancer therapy.

Nat Rev Drug Discov. 2024-4

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RNA interference in the era of nucleic acid therapeutics.

Nat Biotechnol. 2024-3

[6]
Can autoimmune diseases be cured? Scientists see hope at last.

Nature. 2024-1

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Lymph node macrophages drive innate immune responses to enhance the anti-tumor efficacy of mRNA vaccines.

Mol Ther. 2024-3-6

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Lancet. 2023-11-25

[10]
Therapeutic induction of antigen-specific immune tolerance.

Nat Rev Immunol. 2024-5

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