Salari Farhad, Vahedi Fatemeh, Varasteh Abdol-Reza, Ketabdar Hanieh, Chamani Jamshidkhan, Sankian Mojtaba
Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, Hamilton, Ontario, Canada; Biotechnology Department, Razi Vaccine and Serum Research Institute, Mashhad, Iran.
Int Immunopharmacol. 2017 Jul;48:118-125. doi: 10.1016/j.intimp.2017.04.011. Epub 2017 May 11.
Allergen-specific sublingual immunotherapy (SLIT) is well known as an effective and non-invasive route to induce allergy desensitization. The goal of this study was to investigate whether a TAT-fused recombinant allergen could enhance SLIT efficacy. BALB/c mice sensitized to the main allergen (Che a 3) of Chenopodium album pollen were treated sublingually either with rChe a 3 (100μg/dose) or rTAT-Che a 3 (100μg/dose), two times per week for eight weeks. SLIT with rTAT-Che a 3 led to significantly greater allergen-specific IgG2a than rChe a 3; however, neither rTAT-Che a 3 nor rChe a 3 affected allergen-specific IgE or IgG1 antibody levels. In addition, interleukin 4 (IL-4) levels in re-stimulated splenocytes from the rTAT-Che a 3 mice were significantly lower than in those from the rChe a 3 mice, while interferon-γ (IFN-γ) was significantly greater in the rChe a 3 mice than in the rTAT-Che a 3 mice. Furthermore, sublingual administration of rTAT-Che a 3 induced significantly greater TGF-β secretion in re-stimulated splenocytes than administration of rChe a 3. Accordingly, SLIT with rTAT-Che a 3 led to significantly greater expression of TGF-β- and Foxp3-specific mRNAs in the splenocytes than in those from the rChe a 3 mice. Our findings demonstrate that TAT-fused rChe a 3 suppressed the allergic response through preferential enhancement of systemic regulatory T-cell (Treg)-mediated immunity responses, likely by facilitating allergen capture and presentation by sublingual Langerhans-like dendritic cells.
变应原特异性舌下免疫疗法（SLIT）是一种诱导过敏脱敏的有效且非侵入性途径，已广为人知。本研究的目的是探究一种与穿膜肽（TAT）融合的重组变应原是否能增强SLIT疗效。将对藜草花粉主要变应原（Che a 3）致敏的BALB/c小鼠，每周两次舌下给予rChe a 3（100μg/剂量）或rTAT-Che a 3（100μg/剂量），持续八周。与rChe a 3相比，rTAT-Che a 3进行SLIT导致变应原特异性IgG2a显著增加；然而，rTAT-Che a 3和rChe a 3均未影响变应原特异性IgE或IgG1抗体水平。此外，rTAT-Che a 3小鼠再次刺激的脾细胞中白细胞介素4（IL-4）水平显著低于rChe a 3小鼠，而rChe a 3小鼠中的干扰素-γ（IFN-γ）显著高于rTAT-Che a 3小鼠。此外，rTAT-Che a 3舌下给药比rChe a 3给药在再次刺激的脾细胞中诱导出显著更多的转化生长因子-β（TGF-β）分泌。因此，与rChe a 3小鼠相比，rTAT-Che a 3进行SLIT导致脾细胞中TGF-β和Foxp3特异性mRNA的表达显著增加。我们的研究结果表明，与TAT融合的rChe a 3通过优先增强全身调节性T细胞（Treg）介导的免疫反应来抑制过敏反应，可能是通过促进舌下类朗格汉斯树突状细胞捕获和呈递变应原实现的。
