Abstract:
Adjuvants were used to modulate response towards relevant immune cells. The present study aims to investigate FlaA-conjugated Per a 10 and T cell peptides in amelioration of allergic airway disease in mice. Mice given Per a 10 showed allergic features with higher cellular infiltration, IgE, Th-2 cytokines and alarmins. Fusion protein treatment reduced lung inflammation (p < 0.0001) and cellular infiltrates (p < 0.001) with higher IgG2a/IgE indicating resolution of disease. Immunotherapy with FPT1 and FPT3 reduces IL-4, IL-5 and IL-13 levels (p < 0.0001) with a fourfold increase in IFN-γ secretion in BALF. FPT1- and FPT3-treated mice have increased IL-10 and TGF-β levels (p < 0.001) with CD4+Foxp3+ T cells (p < 0.01) indicating Treg response. There was enhanced expression of claudin-1 (1.7-fold) and occludin (fourfold) in lungs of FPT1- and FPT3-treated mice with reduced TSLP (p < 0.01) and IL-33 (p < 0.0001) secretion in BALF indicating recovery of epithelial function. Peptide-conjugated FlaA proteins showed protective immunity in mice and have potential for immunotherapy with restoration of cellular function.
摘要:
佐剂用于调节对相关免疫细胞的应答。本研究旨在研究FlaA缀合的Pera10和T细胞肽在改善小鼠过敏性气道疾病中的作用。每10只小鼠表现出过敏特征,细胞浸润较高,IgE,Th-2细胞因子和警报。融合蛋白治疗减少了肺部炎症(p<0.0001)和细胞浸润(p<0.001),较高的IgG2a/IgE表明疾病消退。用FPT1和FPT3的免疫治疗降低IL-4、IL-5和IL-13水平(p<0.0001),BALF中IFN-γ分泌增加四倍。FPT1和FPT3处理的小鼠具有增加的IL-10和TGF-β水平(p<0.001),其中CD4+Foxp3+T细胞(p<0.01)指示Treg应答。在BALF中TSLP(p<0.01)和IL-33(p<0.0001)分泌减少的FPT1和FPT3处理的小鼠的肺中claudin-1(1.7倍)和occludin(四倍)的表达增强,表明上皮功能恢复。肽偶联的FlaA蛋白在小鼠中显示出保护性免疫力,并具有恢复细胞功能的免疫疗法的潜力。