Adhesive substrate-modulation of adaptive immune responses
Adhesive substrate-modulation of adaptive immune responses
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DOI：
10.1016/j.biomaterials.2008.08.040
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发表时间：
2008-12-01
期刊：
影响因子：
14
通讯作者：
Keselowsky, Benjamin G.
中科院分区：
文献类型：
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作者：
Acharya, Abhinav P.;Dolgova, Natalia V.;Keselowsky, Benjamin G.
虽然众所周知，吸附在植入的生物材料上的蛋白质调节炎症反应，但通过粘附依赖性信号传导对树突状细胞（DC）的调节才刚刚开始被表征。在这项工作中，我们证明了粘附基质引起差异DC成熟和适应性免疫反应。我们发现，粘合剂基板支持类似水平的DC粘附和刺激分子和共刺激分子的表达。相反，DC形态和促炎细胞因子和抗炎细胞因子（分别为IL-12 p40和IL-10）的差异产生是粘附基质依赖性的。例如，在胶原蛋白和玻连蛋白基质上培养的DC产生更高水平的IL-12 p40，而在白蛋白和血清包被的组织培养物处理的基质上培养的DC与其他基质相比产生更高水平的IL-10。此外，我们的研究结果表明，DC介导的同种异体CD 4（+）T细胞增殖和T辅助细胞类型反应的底物依赖性趋势。具体来说，我们发现DC IL-12 p40细胞因子产生的底物依赖性调节与CD 4（+）T细胞增殖和T（h）1型反应（IFN-γ产生的T辅助细胞）相关。此外，我们的结果表明DC介导的刺激产生IL-4的T细胞的底物依赖性趋势，但这种T（h）2型反应不依赖于DC产生IL-10细胞因子。这项工作的影响，在合理设计的生物材料的不同应用，如组织工程的结构，合成的颗粒为基础的疫苗和离体培养的DCS的免疫治疗。(c)2008爱思唯尔有限公司保留所有权利。
While it is well-known that adsorbed proteins on implanted biomaterials modulate inflammatory responses, modulation of dendritic cells (DCs) via adhesion-dependent signaling has only been begun to be characterized. In this work, we demonstrate that adhesive substrates elicit differential DC maturation and adaptive immune responses. We find that adhesive substrates support similar levels of DC adhesion and expression of stimulatory and co-stimulatory molecules. Conversely, DC morphology and differential production of pro- and anti-inflammatory cytokines (IL-12p40 and IL-10, respectively) is adhesive substrate-dependent. For example, DCs cultured on collagen and vitronectin substrates generate higher levels of IL-12p40, whereas DCs Cultured on albumin and serum-coated tissue culture-treated substrates produce the higher levels of IL-10 compared to other substrates. Additionally, our results suggest substrate-dependent trends in DC-mediated allogeneic CD4(+) T-cell Proliferation and T-helper cell type responses. Specifically, we show that substrate-dependent modulation of DC IL-12p40 cytokine production correlates with CD4(+) T-cell proliferation and T(h)1 type response in terms of IFN-gamma producing T-helper cells. Furthermore, our results suggest substrate-dependent trends in DC-mediated stimulation of IL-4 producing T-cells, but this T(h)2 type response is not dependent on DC production of IL-10 cytokine. This work has impact in the rational design of biomaterials for diverse applications such as tissue-engineered constructs, synthetic particle-based vaccines and the ex vivo culture of DCS for immunotherapies. (c) 2008 Elsevier Ltd. All rights reserved.