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解析实验性关节炎中的脂质介质谱分析,研究 resolvin D5 对 T 细胞分化和破骨细胞生成的影响。

Effect of resolvin D5 on T cell differentiation and osteoclastogenesis analyzed by lipid mediator profiling in the experimental arthritis.

机构信息

Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe, Japan.

Department of Clinical Laboratory, Kobe University Hospital, Kobe, Japan.

出版信息

Sci Rep. 2021 Aug 27;11(1):17312. doi: 10.1038/s41598-021-96530-1.

Abstract

Resolvins, are specialized pro-resolving mediators (SPMs) derived from n-3 polyunsaturated fatty acids. They contribute actively to the resolution of inflammation, but little is known concerning their role in chronic inflammation, such as in rheumatoid arthritis (RA). Here, we performed lipid mediator (LM) profiling in tissues from the paws of SKG arthritic mice using lipid chromatography (LC)/mass spectrometry (MS)/MS-based LM metabololipidomics. We found elevated levels of SPMs including resolvin D5 (RvD5) in these tissues. Moreover, RvD5 levels were significantly correlated with arthritis disease activity. From experiments to assess the role of RvD5 in the pathology of RA, we concluded that RvD5 suppressed Th17 cell differentiation and facilitated regulatory T cell differentiation, as well as inhibiting CD4 T cell proliferation. Furthermore, RvD5 attenuated osteoclast differentiation and interfered with osteoclastogenesis. Targeting the resolution of inflammation could be promising as a novel treatment for RA.

摘要

消退素是一类来源于 n-3 多不饱和脂肪酸的特异性促炎消退介质(SPM)。它们积极参与炎症消退,但关于它们在慢性炎症(如类风湿性关节炎(RA))中的作用知之甚少。在这里,我们使用基于脂质色谱(LC)/质谱(MS)/MS 的脂质代谢组学对 SKG 关节炎小鼠爪子中的组织进行了脂质介质(LM)分析。我们发现这些组织中 SPMs(包括消退素 D5(RvD5))的水平升高。此外,RvD5 水平与关节炎疾病活动度呈显著相关。从评估 RvD5 在 RA 病理中的作用的实验中,我们得出结论,RvD5 抑制 Th17 细胞分化并促进调节性 T 细胞分化,同时抑制 CD4 T 细胞增殖。此外,RvD5 减弱破骨细胞分化并干扰破骨细胞形成。针对炎症消退可能是一种有前途的 RA 新疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cb7/8397777/7497c0f77856/41598_2021_96530_Fig1_HTML.jpg

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