强直性脊柱炎中的fox01 - sirt1轴：连接免疫代谢、氧化应激和骨重塑的跨平台调节因子

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews Pub Date : 2025-07-14 DOI:10.1016/j.autrev.2025.103878

Xuhong Zhang, Lu Jia, Xueni Lin, Lamei Zhou

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引用次数: 0

摘要

强直性脊柱炎（AS）是一种慢性免疫介导的疾病，由炎症性骨侵蚀和异位新骨形成的矛盾耦合所定义。最近的研究表明叉头盒O1 (FOXO1)- SIRT1 （SIRT1）信号轴是一个系统水平的调节因子，整合了免疫代谢、氧化还原平衡和骨骼重塑。FOXO1和SIRT1通过转录、表观遗传和代谢途径协同调节免疫耐受、氧化还原平衡和骨骼稳态。本文综述了fox01 - sirt1轴在三个相互关联的模块中的跨平台作用：免疫细胞代谢和极化的调节；自噬和有丝自噬的氧化还原传感和细胞器质量控制炎症微环境中成骨细胞-破骨细胞动力学的协调。该轴的失调破坏免疫代谢平衡，促进病理性骨化，导致AS的双重病理。我们进一步讨论了新兴的治疗策略，从SIRT1激活剂和抗白细胞介素-17 A （IL-17 A）生物制剂到组蛋白去乙酰化酶抑制剂，它们在机制上聚集在fox01 -SIRT1信号传导上。这些翻译方法强调了轴作为免疫和骨骼动态平衡的跨域整合器的潜力，以及作为精确干预as的有希望的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

The FOXO1-SIRT1 axis in ankylosing spondylitis: A cross-platform regulator linking immunometabolism, oxidative stress, and bone remodeling

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The FOXO1-SIRT1 axis in ankylosing spondylitis: A cross-platform regulator linking immunometabolism, oxidative stress, and bone remodeling

Ankylosing spondylitis (AS) is a chronic immune-mediated disorder defined by the paradoxical coupling of inflammatory bone erosion and ectopic new bone formation. Recent studies implicate the Forkhead box O1 (FOXO1)-Sirtuin 1 (SIRT1) signaling axis as a systems-level regulator integrating immune metabolism, redox balance, and skeletal remodeling. FOXO1 and SIRT1 cooperatively regulate immune tolerance, redox balance, and skeletal homeostasis via transcriptional, epigenetic, and metabolic pathways.

This review delineates the cross-platform roles of the FOXO1-SIRT1 axis across three interrelated modules: regulation of immune cell metabolism and polarization; redox sensing and organelle quality control via autophagy and mitophagy; and coordination of osteoblast – osteoclast dynamics in inflammatory microenvironments. Dysregulation of this axis disrupts immuno-metabolic equilibrium and promotes pathological ossification, contributing to the dual pathology of AS.

We further discuss emerging therapeutic strategies – ranging from SIRT1 activators and anti -Interleukin-17 A (IL-17 A) biologics to histone deacetylase inhibitors – that converge mechanistically on FOXO1-SIRT1 signaling. These translational approaches underscore the axis's potential as a cross-domain integrator of immune and skeletal homeostasis, and as a promising target for precision intervention in AS.

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来源期刊

Autoimmunity reviews 医学-免疫学

CiteScore

24.70

自引率

4.40%

发文量

164

审稿时长

21 days

期刊介绍： Autoimmunity Reviews is a publication that features up-to-date, structured reviews on various topics in the field of autoimmunity. These reviews are written by renowned experts and include demonstrative illustrations and tables. Each article will have a clear "take-home" message for readers. The selection of articles is primarily done by the Editors-in-Chief, based on recommendations from the international Editorial Board. The topics covered in the articles span all areas of autoimmunology, aiming to bridge the gap between basic and clinical sciences. In terms of content, the contributions in basic sciences delve into the pathophysiology and mechanisms of autoimmune disorders, as well as genomics and proteomics. On the other hand, clinical contributions focus on diseases related to autoimmunity, novel therapies, and clinical associations. Autoimmunity Reviews is internationally recognized, and its articles are indexed and abstracted in prestigious databases such as PubMed/Medline, Science Citation Index Expanded, Biosciences Information Services, and Chemical Abstracts.