Mitochondrial DNA Sensing Pathogen Recognition Receptors in Systemic Sclerosis Associated Interstitial Lung Disease: A Review.

IF 2.6 2区物理与天体物理 Q2 OPTICS

Physical Review a Pub Date : 2023-12-01 Epub Date: 2023-08-08 DOI:10.1007/s40674-023-00211-1

Alexander Ghincea, Samuel Woo, Sheeline Yu, Taylor Pivarnik, Vitoria Fiorini, Erica L Herzog, Changwan Ryu

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引用次数: 0

Abstract

Purpose of the review: Systemic sclerosis (SSc) is a condition of dermal and visceral scar formation characterized by immune dysregulation and inflammatory fibrosis. Approximately 90% of SSc patients develop interstitial lung disease (ILD), and it is the leading cause of morbidity and mortality. Further understanding of immune-mediated fibroproliferative mechanisms has the potential to catalyze novel treatment approaches in this difficult to treat disease.

Recent findings: Recent advances have demonstrated the critical role of aberrant innate immune activation mediated by mitochondrial DNA (mtDNA) through interactions with toll-like receptor 9 (TLR9) and cytosolic cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS).

Summary: In this review, we will discuss how the nature of the mtDNA, whether oxidized or mutated, and its mechanism of release, either intracellularly or extracellularly, can amplify fibrogenesis by activating TLR9 and cGAS, and the novel insights gained by interrogating these signaling pathways. Because the scope of this review is intended to generate hypotheses for future research, we conclude our discussion with several important unanswered questions.

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系统性硬化症相关间质性肺病中的线粒体 DNA 感知病原体识别受体：综述。

综述的目的：系统性硬化症（SSc）是一种以免疫失调和炎症纤维化为特征的真皮和内脏瘢痕形成病症。约 90% 的系统性硬化症患者会患上间质性肺病 (ILD)，这是发病和死亡的主要原因。对免疫介导的纤维增生机制的进一步了解有可能催生治疗这种难治疾病的新方法：最近的研究进展表明，线粒体 DNA（mtDNA）通过与收费样受体 9（TLR9）和胞浆环鸟苷酸-单磷酸腺苷合成酶（cGAS）相互作用，介导先天性免疫异常激活起着至关重要的作用。摘要：在这篇综述中，我们将讨论 mtDNA 的性质（无论是氧化还是突变）及其在细胞内或细胞外的释放机制如何通过激活 TLR9 和 cGAS 来扩大纤维化，以及通过研究这些信号通路所获得的新见解。由于本综述的目的是为未来研究提出假设，因此我们在讨论的最后提出了几个重要的未决问题。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Physical Review a OPTICSPHYSICS, ATOMIC, MOLECULAR & CHEMICA-PHYSICS, ATOMIC, MOLECULAR & CHEMICAL

CiteScore

5.30

自引率

24.10%

发文量

2086

期刊介绍： Physical Review A (PRA) publishes important developments in the rapidly evolving areas of atomic, molecular, and optical (AMO) physics, quantum information, and related fundamental concepts. PRA covers atomic, molecular, and optical physics, foundations of quantum mechanics, and quantum information, including: -Fundamental concepts -Quantum information -Atomic and molecular structure and dynamics; high-precision measurement -Atomic and molecular collisions and interactions -Atomic and molecular processes in external fields, including interactions with strong fields and short pulses -Matter waves and collective properties of cold atoms and molecules -Quantum optics, physics of lasers, nonlinear optics, and classical optics