Assessing the immunopotency of Toll-like receptor agonists in an in vitro tissue-engineered immunological model

	Assessing the immunopotency of Toll-like receptor agonists in an in vitro tissue-engineered immunological model
	Ma, Yifan; Poisson, Louis; Sanchez-Schmitz, Guzman
刊名	IMMUNOLOGY
	2010
卷号	130 期号:3 页码:374-384
英文摘要	P>The in vitro Peripheral Tissue Equivalent (PTE) module is a three-dimensional tissue-engineered endothelial cell/collagen matrix culture system, which has been reported to reproduce in vivo physiological conditions and which generates dendritic cells (DC) autonomously. In the present study, we used the PTE module to investigate the immunopotency of Toll-like receptor (TLR) agonists, including polyinosine-polycytidylic acid, Gardiquimod, CpG 2006 and lipopolysaccharide. Application of TLR agonists in the PTE module induced a wide range of cytokines, including interleukins 1 alpha/beta, 6, 8 and 10 and tumour necrosis factor-alpha. Compared with traditional peripheral blood mononuclear cell (PBMC) cultures, the PTE module produced twofold to 100-fold higher levels of cytokine secretion, indicating that it can be a highly sensitive assay system. This increased sensitivity is the result of the natural synergy between the leucocytes and the endothelium. Furthermore, the application of TLR agonists, such as lipopolysaccharide and Gardiquimod, to the PTE module enhanced DC differentiation and promoted DC maturation, as indicated by up-regulated expression of CD83, CD86 and CCR7(CD197). In addition, functional assays indicated PTE-derived DC treated with Gardiquimod, a TLR-7 agonist, significantly augmented anti-tetanus toxoid antibody production. Interestingly, replacing PBMC with purified myeloid cells (CD33+) significantly reduced the responsiveness of the PTE module to TLR stimulation. The reduced sensitivity was partly the result of the removal of plasmacytoid DC that participated in the response to TLR stimulation and sensitization of the PTE module. Overall, the in vitro PTE module clearly demonstrated the effects of TLR agonists on DC generation, maturation and antigen-presenting capacity, and may serve as a sensitive and predictive test bed for the evaluation of adjuvant candidates.
收录类别	SCI
原文出处	http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2567.2009.03237.x/epdf
语种	英语
内容类型	期刊论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/2909]
专题	深圳先进技术研究院_医工所
作者单位	IMMUNOLOGY
推荐引用方式 GB/T 7714	Ma, Yifan,Poisson, Louis,Sanchez-Schmitz, Guzman. Assessing the immunopotency of Toll-like receptor agonists in an in vitro tissue-engineered immunological model[J]. IMMUNOLOGY,2010,130(3):374-384.
APA	Ma, Yifan,Poisson, Louis,&Sanchez-Schmitz, Guzman.(2010).Assessing the immunopotency of Toll-like receptor agonists in an in vitro tissue-engineered immunological model.IMMUNOLOGY,130(3),374-384.
MLA	Ma, Yifan,et al."Assessing the immunopotency of Toll-like receptor agonists in an in vitro tissue-engineered immunological model".IMMUNOLOGY 130.3(2010):374-384.