Datos relacionados al estudio de las propiedades inmunomoduladoras de Prosopis strombulifera

Background: New products with tolerogenic properties on T cell response are necessary to improve current efficacy, cost and side effects of immunosuppressants. Prosopis strombulifera aqueous extract (PsAE) have reported cytotoxic, antitumoral, antiatherogenic and antileishmanial activities, containing phytochemicals with immune-related activities. Despite these, there are no previous studies with respect to PsAE suppressive properties over T cell proliferation and their function. Goal: Because of previous antecedents, this study aims to evaluate the effect of PsAE on T cell activation, proliferation, cytokine production, and to investigate its effect over an in vivo model of type 1 diabetes (T1D). Experimental procedure: Splenocytes and sorted CD4þ/CD8þ from wild type C57BL/6 mice were cultured to determine activation, IFN-g release and T-cell proliferation after polyclonal stimulation. NOD (nonobese diabetic) mice were used to study the effects of orally administered extract on glycemia, insulitis stages and perforin-1 (PRF-1)/granzyme-B (GRZ-B) expression. Results: In primary cultures, the plant extract impairs T cell activation, decreases IFN-g release, and reduces proliferation after different polyclonal stimuli. In vivo, PsAE improves NOD mice glycemic levels and T1D progression by diminution of pancreas insulitis and reduction of PRF-1 and GRZ-B mRNA expression. To our knowledge, this is the first report characterizing the therapeutic properties of PsAE on T cell activation. Conclusion: The current work provides evidence about in vitro and in vivo immunosuppressive effects of PsAE and promotes this plant extract as a complementary and alternative treatment in autoimmune Tcell mediated diseases as T1D.

背景：为了提升现有免疫抑制剂在疗效、成本及副作用方面的表现，迫切需要开发具有免疫耐受特性的新型产品。金合欢属植物 Prosopis strombulifera 的水提物（PsAE）已被报道具有细胞毒性、抗肿瘤、抗动脉粥样硬化和抗利什曼原虫活性，其中含有与免疫相关活性的植物化学成分。尽管如此，关于PsAE对T细胞增殖的抑制特性及其功能尚无先例研究。目标：鉴于前人的研究基础，本研究旨在评估PsAE对T细胞活化、增殖、细胞因子产生的影响，并探究其在1型糖尿病（T1D）体内模型中的效果。实验流程：从野生型C57BL/6小鼠的脾细胞中分离出CD4þ/CD8þ T细胞进行培养，以确定经多克隆刺激后的活化、IFN-g释放和T细胞增殖。使用NOD（非肥胖型糖尿病）小鼠研究口服提取物的效果，包括血糖水平、胰岛炎阶段及穿孔素-1（PRF-1）/颗粒酶B（GRZ-B）的表达。结果：在原代培养中，植物提取物损害了T细胞活化，降低了IFN-g的释放，并在不同多克隆刺激后减少了增殖。在体内实验中，PsAE通过减轻胰腺胰岛炎和降低PRF-1和GRZ-B mRNA表达，改善了NOD小鼠的血糖水平和T1D进程。据我们所知，这是首次报道PsAE对T细胞活化治疗特性的研究。结论：本研究提供了关于PsAE在体外和体内免疫抑制效果的证据，并推荐该植物提取物作为治疗T细胞介导的自身免疫性疾病，如T1D的辅助和替代疗法。