破解 1 型糖尿病密码:基因、微生物、免疫力和早期生活环境

IF 7.5 2区 医学 Q1 IMMUNOLOGY
Christopher Yau, Jayne S. Danska
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引用次数: 0

摘要

摘要1型糖尿病(T1D)是由遗传易感性、免疫失调和环境诱因等复杂因素相互作用的结果,最终导致分泌胰岛素的胰腺β细胞遭到破坏。本综述全面探讨了导致 T1D 发病的多种因素,以阐明其关键机制和潜在的治疗靶点。我们首先探讨了遗传风险因素,剖析了与 T1D 易感性相关的人类白细胞抗原 (HLA) 单倍型和非 HLA 基因变异的作用。从 NOD 小鼠模型中获得的机理认识为人类疾病提供了有价值的相似之处,尤其是β细胞引导的自身免疫背后的免疫学复杂性。研究探讨了T1D发病机制的免疫学驱动因素,强调了效应T细胞和调节T细胞的关键作用,以及B细胞和自身抗体在β细胞破坏中的多重功能。此外,还研究了环境风险因素的影响,特别是肠道微生物组对宿主免疫发展的调节作用。最后,该综述探讨了人类纵向研究,揭示了粘膜免疫、全身抗微生物抗体反应和 T1D 发展轨迹之间的动态相互作用。从这些相互关联的因素中获得的启示为采取有针对性的干预措施和确定生物标志物以加强 T1D 管理和预防策略铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Cracking the type 1 diabetes code: Genes, microbes, immunity, and the early life environment

Cracking the type 1 diabetes code: Genes, microbes, immunity, and the early life environment

Type 1 diabetes (T1D) results from a complex interplay of genetic predisposition, immunological dysregulation, and environmental triggers, that culminate in the destruction of insulin-secreting pancreatic β cells. This review provides a comprehensive examination of the multiple factors underpinning T1D pathogenesis, to elucidate key mechanisms and potential therapeutic targets. Beginning with an exploration of genetic risk factors, we dissect the roles of human leukocyte antigen (HLA) haplotypes and non-HLA gene variants associated with T1D susceptibility. Mechanistic insights gleaned from the NOD mouse model provide valuable parallels to the human disease, particularly immunological intricacies underlying β cell–directed autoimmunity. Immunological drivers of T1D pathogenesis are examined, highlighting the pivotal contributions of both effector and regulatory T cells and the multiple functions of B cells and autoantibodies in β-cell destruction. Furthermore, the impact of environmental risk factors, notably modulation of host immune development by the intestinal microbiome, is examined. Lastly, the review probes human longitudinal studies, unveiling the dynamic interplay between mucosal immunity, systemic antimicrobial antibody responses, and the trajectories of T1D development. Insights garnered from these interconnected factors pave the way for targeted interventions and the identification of biomarkers to enhance T1D management and prevention strategies.

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来源期刊
Immunological Reviews
Immunological Reviews 医学-免疫学
CiteScore
16.20
自引率
1.10%
发文量
118
审稿时长
4-8 weeks
期刊介绍: Immunological Reviews is a specialized journal that focuses on various aspects of immunological research. It encompasses a wide range of topics, such as clinical immunology, experimental immunology, and investigations related to allergy and the immune system. The journal follows a unique approach where each volume is dedicated solely to a specific area of immunological research. However, collectively, these volumes aim to offer an extensive and up-to-date overview of the latest advancements in basic immunology and their practical implications in clinical settings.
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