健康、自身炎症和自身免疫疾病中的 DNA 传感途径

IF 27.7 1区医学 Q1 IMMUNOLOGY

Nature Immunology Pub Date : 2024-10-04 DOI:10.1038/s41590-024-01966-y

Mingqi Dong, Katherine A. Fitzgerald

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引用次数: 0

摘要

检测微生物 DNA 是宿主防御的主要手段。在哺乳动物细胞中，DNA 传感途径可诱导强有力的抗微生物反应，启动适应性免疫，最终清除感染病原体。然而，大多数 DNA 传感器的识别机制与序列无关，这在赋予其广泛检测能力优势的同时，也给哺乳动物细胞在平衡状态下保持对自身 DNA 的无知带来了巨大挑战。在这篇综述中，我们总结了DNA感应途径的基本原理，以及使这些途径处于受控状态的错综复杂的调控网络。此外，我们还描述了调控约束如何会出现缺陷，并成为人类自身炎症和自身免疫疾病的基础。此外，我们还讨论了正在开发的疗法，这些疗法可限制由自身 DNA 或 DNA 传感通路的不适当激活引发的炎症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

DNA-sensing pathways in health, autoinflammatory and autoimmune diseases

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DNA-sensing pathways in health, autoinflammatory and autoimmune diseases

Detection of microbial DNA is a primary means of host defense. In mammalian cells, DNA-sensing pathways induce robust anti-microbial responses and initiation of adaptive immunity, leading to the eventual clearance of the infectious agent. However, while conferring the advantage of broad detection capability, the sequence-independent recognition mechanisms of most DNA sensors pose a significant challenge for mammalian cells to maintain ignorance to self-DNA under homeostatic conditions. In this Review, we summarize the fundamentals of DNA-sensing pathways and the intricate regulatory networks that keep these pathways in check. In addition, we describe how regulatory restraints can be defective and underlie human autoinflammatory and autoimmune diseases. Further, we discuss therapies in development that limit inflammation fueled by self-DNA or inappropriate activation of DNA-sensing pathways. In this Review, Fitzgerald and Dong summarize the fundamentals of DNA-sensing pathways in health, autoinflammatory and autoimmune diseases.

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来源期刊

Nature Immunology 医学-免疫学

CiteScore

40.00

自引率

2.30%

发文量

248

审稿时长

4-8 weeks

期刊介绍： Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.