Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Respirology. 2014 Jan;19(1):122-31. doi: 10.1111/resp.12198.
Previous studies have demonstrated that our recombinant bacille Calmette-Guerin (rBCG), which expresses Der p2 in house dust mite (Der p2 rBCG) suppresses asthmatic airway inflammation by regulating the phenotype and function of dendritic cells (DC) and reprogramming T helper (Th) 0 cell differentiation into different T cell (Th1/Th2/Treg) subtypes. However, the exact role of Der p2 rBCG in reprogramming Th17 differentiation and the relevant mechanisms are not known. The aim of this study was to examine whether Der p2 rBCG-mediated inhibition of allergic airway inflammation is mediated by regulating Th17 differentiation in a murine asthma model.
Primary mouse bone marrow-derived dendritic cells (BMDC) were infected with Der p2 rBCG and adoptively transferred to Der p2-intranasally sensitized mice. The role of Der p2 rBCG-BMDC on the regulation of airway inflammation and Th17 cell differentiation was assessed.
Adoptive transfer of Der p2 rBCG-BMDC suppressed airway inflammation and mucin secretion. Der p2 rBCG-BMDC inhibited excessive Th17 immune responses but not BCG-BMDC. Furthermore, Der p2 rBCG decreased jagged-2 and increased delta-like-4 expressions on BMDC to a greater extent than BCG.
These findings suggest that DC plays a key role in Der p2 rBCG-induced immunoregulation. Der p2 rBCG also displayed a potent inhibitory effect on Th17 differentiation, and these findings increase our understanding of the cellular basis of Der p2 BCG-mediated inhibition of asthma.
先前的研究表明,我们表达屋尘螨 Der p2 的重组卡介苗(rBCG)通过调节树突状细胞(DC)的表型和功能以及重编程辅助性 T 细胞(Th)0 细胞分化为不同的 T 细胞(Th1/Th2/Treg)亚型来抑制哮喘气道炎症。然而,Der p2 rBCG 重编程 Th17 分化的确切作用及其相关机制尚不清楚。本研究旨在探讨 Der p2 rBCG 介导的抑制变应性气道炎症是否通过调节小鼠哮喘模型中的 Th17 分化来实现。
用 Der p2 rBCG 感染原代小鼠骨髓来源的树突状细胞(BMDC),并将其过继转移至 Der p2 经鼻内致敏的小鼠。评估 Der p2 rBCG-BMDC 对气道炎症和 Th17 细胞分化的调节作用。
过继转移 Der p2 rBCG-BMDC 可抑制气道炎症和黏蛋白分泌。Der p2 rBCG-BMDC 抑制过度的 Th17 免疫反应,但不抑制 BCG-BMDC。此外,与 BCG 相比,Der p2 rBCG 使 BMDC 上 jagged-2 的表达降低,delta-like-4 的表达增加。
这些发现表明 DC 在 Der p2 rBCG 诱导的免疫调节中起关键作用。Der p2 rBCG 还对 Th17 分化显示出强大的抑制作用,这些发现增加了我们对 Der p2 BCG 介导的哮喘抑制的细胞基础的理解。