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