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TGFβ1 mimetic peptide modulates immune response to grass pollen allergens in mice

机译:TGFβ1模拟肽调节对小鼠的草花粉过敏原的免疫应答

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Abstract Background Transforming growth factor β1 (TGFβ1) is a cytokine that exerts immunosuppressive functions, as reflected by its ability to induce regulatory T (Treg) cell differentiation and inhibit Th1 and Th2 responses. Hence, peptides that mimic the active core domain of TGFβ1 may be promising candidates for modulation of the allergic response. This study aimed to investigate a synthetic TGFβ1 mimetic peptide (TGFβ1‐mim) for its ability to modulate the immune response during allergic sensitization to grass pollen allergens. Methods The in vitro action of TGFβ1‐mim was evaluated in human lung epithelial cells, Jurkat cells, and rat basophilic leukemia cells. The in vivo action was evaluated in a murine model of Phl p 5 allergic sensitization. Additionally, the Th2 modulatory response was evaluated in IL‐4 reporter mice. Results In vitro, TGFβ1‐mim downregulated TNF‐α production, IL‐8 gene expression, and cytokine secretion, upregulated IL‐10 secretion, and inhibited Phl p 5‐induced basophil degranulation. During Phl p 5 sensitization in mice, TGFβ1‐mim downregulated IL‐2, IL‐4, IL‐5, IL‐13, and IFN‐γ, upregulated IL‐10, and induced Treg cell production. Furthermore, mice treated with TGFβ1‐mim had lower levels of IgE, IgG1, IgG2a and higher levels of IgA antibodies than control mice. In a reporter mouse, the mimetic inhibited Th2 polarization. Conclusion The TGFβ1‐mim efficiently modulated various important events that exacerbate the allergic microenvironment, including the production of main cytokines that promote Th1 and Th2 differentiation, and the induction of allergen‐specific regulatory T cells, highlighting its potential use in therapeutic approaches to modulate the immune response toward environmental allergens.
机译:摘要背景改变生长因子β1(TGFβ1)是一种细胞因子,其施加免疫抑制功能,如其诱导调节性T(Treg)细胞分化和抑制Th1和Th2反应的能力。因此,模拟TGFβ1的活性核结构域的肽可能是用于调节过敏反应的候选者。本研究旨在探讨合成的TGFβ1模拟肽(TGFβ1-MIM),以便其调节过敏性敏感过程中对草花粉过敏原的免疫应答。方法在人肺上皮细胞,Jurkat细胞和大鼠嗜碱性白血病细胞中评估TGFβ1-MIM的体外作用。在PHL P 5过敏敏化的小鼠模型中评估体内作用。另外,在IL-4报告小鼠中评价TH2调节响应。结果在体外,TGFβ1-MIM下调TNF-α生产,IL-8基因表达和细胞因子分泌,上调IL-10分泌,并抑制PHL P 5诱导的嗜碱性粒子溶液。在PHL P 5期间小鼠的致敏期间,TGFβ1-MIM下调IL-2,IL-4,IL-5,IL-13和IFN-γ,上调的IL-10和诱导的Treg细胞产生。此外,用TGFβ1-MIM处理的小鼠具有比对照小鼠更低的IgE,IgG1,IgG2a和更高水平的IgA抗体。在报告小鼠中,模拟抑制Th2极化。结论TGFβ1-MIM有效地调节加剧过敏微环境的各种重要事件,包括促进促进TH1和TH2分化的主要细胞因子,以及诱导过敏原特异性调节性T细胞的诱导,突出其在治疗方法中的潜在用途来调节对环境过敏原的免疫反应。

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