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舌下给予聚(乳酸-共-乙醇酸)(PLGA)包裹变应原下调 BALB/c 小鼠的 Th2 免疫应答。

Down-regulation of Th2 immune responses by sublingual administration of poly (lactic-co-glycolic) acid (PLGA)-encapsulated allergen in BALB/c mice.

机构信息

Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Allergy Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Int Immunopharmacol. 2015 Dec;29(2):672-678. doi: 10.1016/j.intimp.2015.09.011. Epub 2015 Sep 26.

Abstract

The goal of this study was to investigate whether poly (lactic-co-glycolic) acid (PLGA) nanoparticles could enhance sublingual immunotherapy (SLIT) efficacy. BALB/c mice sensitized to rChe a 3 were treated sublingually either with soluble rChe a 3 (100μg/dose) or PLGA-encapsulated rChe a 3 (5, 25, or 50μg/dose). SLIT with PLGA-encapsulated rChe a 3 (equivalent to 25 and 50μg rChe a 3 per dose) led to significantly increased antigen-specific IgG2a, along with no effect on allergen-specific IgE and IgG1 antibody levels. In addition, interleukin 4 (IL-4) levels in restimulated splenocytes were significantly less, while interferon-γ (IFN-γ), interleukin-10 (IL-10), and transforming growth factor-β (TGF-β) levels, as well as Foxp3 expression, were significantly greater than in the control groups. Our findings suggest that PLGA nanoparticle-based vaccination may help rational development of sublingual immunotherapy through reduction of the needed allergen doses and also significantly enhanced systemic T regulatory (Treg) and T helper 1 (Th1) immune responses.

摘要

本研究旨在探讨聚(丙交酯-共-乙交酯)(PLGA)纳米粒能否增强舌下免疫疗法(SLIT)的疗效。将 BALB/c 小鼠致敏于 rChe a 3 后,通过舌下给予可溶性 rChe a 3(100μg/剂量)或 PLGA 包裹的 rChe a 3(5、25 或 50μg/剂量)。用 PLGA 包裹的 rChe a 3(相当于每剂量 25 和 50μg rChe a 3)进行 SLIT 导致抗原特异性 IgG2a 显著增加,而对过敏原特异性 IgE 和 IgG1 抗体水平没有影响。此外,在再刺激的脾细胞中,白细胞介素 4(IL-4)水平显著降低,而干扰素-γ(IFN-γ)、白细胞介素 10(IL-10)和转化生长因子-β(TGF-β)水平以及 Foxp3 表达显著高于对照组。我们的研究结果表明,基于 PLGA 纳米粒的疫苗接种可能有助于通过减少所需过敏原剂量,以及显著增强系统性调节性 T 细胞(Treg)和辅助性 T 细胞 1(Th1)免疫反应,合理地开发舌下免疫疗法。

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