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Tuftsin 磷酸胆碱——一种利用寄生虫来对抗自身免疫的新型化合物。

Tuftsin phosphorylcholine-a novel compound harnessing helminths to fight autoimmunity.

机构信息

Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, affiliated with the Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.

Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

出版信息

Immunol Res. 2018 Dec;66(6):637-641. doi: 10.1007/s12026-018-9051-2.

DOI:10.1007/s12026-018-9051-2
PMID:30554380
Abstract

The distinction that in areas where helminthic infections are common, autoimmune diseases are less prevalent, led to the investigation of immune modulatory properties of helminths and their derivatives. Such are phosphorylcholine (PC) moieties which are a component of secreted products of helminths. PC has been broadly studied for its attenuating effects on the human immune system. In an attempt to develop a novel therapeutic small molecule for the treatment of autoimmune conditions, we have conjugated PC with tuftsin, a natural immunomodulatory tetrapeptide, to create TPC. Herein, we review our findings regarding the effects of TPC in murine models of three autoimmune diseases-systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and rheumatic arthritis (RA), as well as ex-vivo samples from giant cell arteritis (GCA) patients. In all four disease models examined, TPC was shown to attenuate the inflammatory response by reducing expression of pro-inflammatory cytokines and altering the phenotype of T cell expression. In murine models, TPC has further produced a significant improvement in clinical disease scores with no significant side effects noted. Our findings suggest TPC presents promising potential as a novel therapeutic agent for the effective treatment of various autoimmune conditions.

摘要

在寄生虫感染较为常见的地区,自身免疫性疾病的发病率较低,这一现象促使人们对寄生虫及其衍生物的免疫调节特性进行了研究。例如,磷酸胆碱(PC)是寄生虫分泌产物的一个组成部分。PC 因其对人体免疫系统的减弱作用而被广泛研究。为了开发一种治疗自身免疫性疾病的新型治疗性小分子药物,我们将 PC 与 tuftsin(一种天然免疫调节四肽)偶联,形成 TPC。在此,我们回顾了 TPC 在三种自身免疫性疾病(系统性红斑狼疮(SLE)、炎症性肠病(IBD)和风湿性关节炎(RA))的小鼠模型以及巨细胞动脉炎(GCA)患者的体外样本中的作用。在所有四种疾病模型中,TPC 通过降低促炎细胞因子的表达和改变 T 细胞表达的表型,来减轻炎症反应。在小鼠模型中,TPC 进一步显著改善了临床疾病评分,且没有明显的副作用。我们的研究结果表明,TPC 具有作为一种治疗各种自身免疫性疾病的新型治疗药物的巨大潜力。

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本文引用的文献

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Tuftsin-phosphorylcholine (TPC) equally effective to methylprednisolone in ameliorating lupus nephritis in a mice model.Tuftsin-磷酸胆碱(TPC)在改善狼疮肾炎的小鼠模型中与甲泼尼龙同样有效。
Clin Exp Immunol. 2018 Aug;193(2):160-166. doi: 10.1111/cei.13137.
2
Tuftsin-phosphorylcholine treatment of autoimmune diseases - a benefit and a message from helminths?吞噬细胞增强因子-磷酸胆碱治疗自身免疫性疾病——一种益处及来自蠕虫的启示?
Reumatologia. 2017;55(6):267-268. doi: 10.5114/reum.2017.72622. Epub 2017 Dec 30.
3
Safety and efficacy of helminth treatment in relapsing-remitting multiple sclerosis: Results of the HINT 2 clinical trial.
银耳多糖和抗原肽联合免疫细胞治疗结直肠癌的疗效。
Med Sci Monit. 2019 Jul 23;25:5465-5472. doi: 10.12659/MSM.915037.
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Editorial: autoimmunity-the ever endless world.社论:自身免疫——永无止境的世界。
Immunol Res. 2018 Dec;66(6):633-636. doi: 10.1007/s12026-019-09071-1.
寄生虫治疗对复发缓解型多发性硬化症的安全性和疗效:HINT 2 临床试验结果。
Mult Scler. 2019 Jan;25(1):81-91. doi: 10.1177/1352458517736377. Epub 2017 Oct 24.
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Tuftsin - Properties and Analogs.吞噬细胞增强因子——特性与类似物。
Curr Med Chem. 2017 Nov 17;24(34):3711-3727. doi: 10.2174/0929867324666170725140826.
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Tuftsin-Phosphorylcholine Maintains Normal Gut Microbiota in Collagen Induced Arthritic Mice.促吞噬素-磷酸胆碱维持胶原诱导性关节炎小鼠的正常肠道微生物群。
Front Microbiol. 2017 Jul 10;8:1222. doi: 10.3389/fmicb.2017.01222. eCollection 2017.
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Are Helminths to be Trusted as Allies in the War against Autoimmunity and Chronic Inflammation?在对抗自身免疫和慢性炎症的战争中,蠕虫能被当作盟友而值得信赖吗?
Isr Med Assoc J. 2016 Mar-Apr;18(3-4):139-40.
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Novel therapeutic compound tuftsin-phosphorylcholine attenuates collagen-induced arthritis.新型治疗化合物促吞噬肽-磷酰胆碱可减轻胶原诱导的关节炎。
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