Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Department of Organic Chemistry, The Weizmann Institute of Sciences, Rehovot, Israel.
J Autoimmun. 2015 May;59:1-7. doi: 10.1016/j.jaut.2015.03.001. Epub 2015 Apr 10.
In areas where helminths infections are common, autoimmune diseases are rare. Treatment with helminths and ova from helminths, improved clinical findings of inflammatory bowel disease, multiple-sclerosis and rheumatoid-arthritis. The immunomodulatory functions of some helminths were attributed to the phosphorylcholine (PC) moiety. We aimed to decipher the tolerogenic potential of Tuftsin-PC (TPC) compound in mice genetically prone to develop lupus. Lupus prone NZBXW/F1 mice received subcutaneously TPC (5 μg/1 ml), 3 times a week starting at 14 weeks age. Autoantibodies were tested by ELISA, T-regulatory-cells by FACS, cytokines profile by RT-PCR and cytokines protein levels by DuoSet ELISA. Glomerulonephritis was addressed by detection of proteinuria, and immunoglobulin complex deposition in the mesangium of the kidneys of the mice by immunofluorescence. Our results show that TPC attenuated the development of glomerulonephritis in lupus prone mice, in particular, it ameliorated proteinuria (p < 0.02), and reduced immunoglobulin deposition in the kidney mesangium. TPC also enhanced the expression of TGFβ and IL-10 (p < 0.001), and inhibited the production of IFNγ and IL-17 (p < 0.03). TPC Significantly enhanced the expansion of CD4+CD25+FOXP3+ T-regulatory cells (Tregs) phenotype in the treated mice. These data indicate that TPC hampered lupus development in genetically lupus prone mice which was exemplified by moderate glomerulonephritis, attenuation of pro-inflammatory cytokines and enhancement of anti-inflammatory cytokines expression, as well as Tregs expansion. Our results propose harnessing novel natural therapy for lupus patients.
在寄生虫感染常见的地区，自身免疫性疾病很少见。寄生虫和寄生虫卵的治疗改善了炎症性肠病、多发性硬化症和类风湿关节炎的临床发现。一些寄生虫的免疫调节功能归因于磷酸胆碱（PC）部分。我们旨在破译 Tuftsin-PC（TPC）化合物在易患狼疮的小鼠中的耐受潜力。狼疮易感 NZBXW/F1 小鼠从 14 周龄开始每周接受 3 次皮下 TPC（5μg/1ml）。通过 ELISA 检测自身抗体，通过 FACS 检测 T 调节细胞，通过 RT-PCR 检测细胞因子谱，通过 DuoSet ELISA 检测细胞因子蛋白水平。通过检测蛋白尿和免疫球蛋白复合物在肾脏肾小球中的沉积来研究肾小球肾炎。我们的结果表明，TPC 减轻了狼疮易感小鼠的肾小球肾炎的发展，特别是改善了蛋白尿（p<0.02），并减少了肾脏肾小球中的免疫球蛋白沉积。TPC 还增强了 TGFβ和 IL-10 的表达（p<0.001），并抑制了 IFNγ和 IL-17 的产生（p<0.03）。TPC 显著增强了治疗小鼠中 CD4+CD25+FOXP3+T 调节细胞（Tregs）表型的扩张。这些数据表明，TPC 阻碍了遗传易患狼疮的小鼠中狼疮的发展，其特征是中度肾小球肾炎、促炎细胞因子的衰减以及抗炎细胞因子表达的增强以及 Tregs 的扩张。我们的结果提出利用新的天然疗法治疗狼疮患者。
