Metabolic Reprogramming in Stromal and Immune Cells in Rheumatoid Arthritis and Osteoarthritis: Therapeutic Possibilities

IF 4.5 3区 医学 Q2 IMMUNOLOGY
Órlaith C. Henry, Luke A. J. O'Neill
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Abstract

Metabolic reprogramming of stromal cells, including fibroblast-like synoviocytes (FLS) and chondrocytes, as well as osteoclasts (OCs), are involved in the inflammatory and degenerative processes underlying rheumatoid arthritis (RA) and osteoarthritis (OA). In RA, FLS exhibit mTOR activation, enhanced glycolysis and reduced oxidative phosphorylation, fuelling inflammation, angiogenesis, and cartilage degradation. In OA, chondrocytes undergo metabolic rewiring, characterised by mTOR and NF-κB activation, mitochondrial dysfunction, and increased glycolysis, which promotes matrix metalloproteinase production, extracellular matrix (ECM) degradation, and angiogenesis. Macrophage-derived immunometabolites, including succinate and itaconate further modulate stromal cell function, acting as signalling molecules that modulate inflammatory and catabolic processes. Succinate promotes inflammation whilst itaconate is anti-inflammatory, suppressing inflammatory joint disease in models. Itaconate deficiency also correlates inversely with disease severity in RA in humans. Emerging evidence highlights the potential of targeting metabolic processes as promising therapeutic strategies for connective tissue disorders.

Abstract Image

类风湿关节炎和骨关节炎中基质和免疫细胞的代谢重编程:治疗的可能性
基质细胞的代谢重编程,包括成纤维细胞样滑膜细胞(FLS)和软骨细胞,以及破骨细胞(OCs),参与类风湿关节炎(RA)和骨关节炎(OA)的炎症和退行性过程。在RA中,FLS表现出mTOR激活、糖酵解增强和氧化磷酸化减少,从而促进炎症、血管生成和软骨降解。在骨性关节炎中,软骨细胞经历代谢重组,其特征是mTOR和NF-κB活化、线粒体功能障碍和糖酵解增加,从而促进基质金属蛋白酶的产生、细胞外基质(ECM)降解和血管生成。巨噬细胞衍生的免疫代谢物,包括琥珀酸盐和衣康酸盐,进一步调节基质细胞功能,作为调节炎症和分解代谢过程的信号分子。琥珀酸盐促进炎症,而衣康酸盐抗炎,抑制炎症性关节疾病。衣康酸缺乏也与人类类风湿性关节炎的疾病严重程度呈负相关。新出现的证据强调了靶向代谢过程作为结缔组织疾病有希望的治疗策略的潜力。
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来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
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