Adhesive substrates modulate the activation and stimulatory capacity of non-obese diabetic mouse-derived dendritic cells
Adhesive substrates modulate the activation and stimulatory capacity of non-obese diabetic mouse-derived dendritic cells
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DOI：
10.1016/j.actbio.2010.08.026
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发表时间：
2011-01-01
影响因子：
9.7
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.
众所周知，植入生物材料上吸附的粘附蛋白调节炎症反应;然而，与粘附蛋白相互作用后树突状细胞（DC）反应的调节才开始被表征。DC是调节先天性和适应性免疫应答的特化抗原呈递细胞。以前，我们已经表明，激活和刺激能力的DC来自C57 BL 6/j小鼠的差异调节的粘附基板。在这里，我们扩大我们的调查，考虑的情况下，与糖尿病相关的成熟缺陷的DC反应的粘附基质调制。了解糖尿病患者DC的粘附反应对于免疫治疗和组织工程应用具有潜在的重要意义。在这项工作中，我们使用非肥胖糖尿病（NOD）小鼠，一种建立的1型糖尿病动物模型，以产生DC（NOD-DC）。我们证明，NOD-DCs培养在不同的粘合剂基板（胶原蛋白，纤维蛋白原，纤连蛋白，层粘连蛋白，玻连蛋白，白蛋白和血清）响应基板依赖性调制的表面表达的刺激分子MHC-II和共刺激分子CD 80和CD 86和生产的细胞因子IL-12 p40和IL-10。此外，NOD-DCs刺激CD 4（+）T细胞增殖和细胞因子（1-4和1FN-γ）产生的能力显示出底物依赖性调节。具体地，在玻连蛋白上培养的NOD-DC诱导最高的IL-12 p40产生，而胶原诱导最高的IL-10产生。在胶原蛋白、纤维蛋白原和血清包被的基质上培养的树突状细胞刺激最高的CD 4（+）T细胞增殖。进一步确定，在玻连蛋白上培养的DC诱导产生IL-4的T细胞的最高百分比群体，并且在纤连蛋白包被的基底上培养的DC诱导T细胞中IFN-γ的最高表达。Pearson相关分析显示T细胞增殖与DC的CD 80表达水平以及T细胞产生IL-4和DC产生IL-10之间具有高度相关性。这种基于底物的NOD-DC激活和刺激能力的控制与非糖尿病B6-DC反应不同，建立了免疫细胞反应的粘附调节领域，并为1型糖尿病患者生物材料的合理设计提供了信息。由Elsevier Ltd.代表Acta Materialia Inc.出版。
It is known that adsorbed adhesive proteins on implanted biomaterials modulate inflammatory responses; however, modulation of dendritic cell (DC) responses upon interaction with adhesive proteins has only begun to be characterized. DCs are specialized antigen-presenting cells that modulate both innate and adaptive immune responses. Previously we have shown that the activation and stimulatory capacity of DCs derived from C57BL6/j mice is differentially modulated by adhesive substrates. Here we extend our investigation of adhesive substrate modulation of DC responses to consider the case where the DCs had maturational defects associated with diabetes. Understanding the adhesive responses of DCs in diabetics is potentially important for immunotherapy and tissue engineering applications. In this work we use the non-obese diabetic (NOD) mouse, an established animal model for type l diabetes, to generate DCs (NOD-DCs). We demonstrate that NOD-DCs cultured on different adhesive substrates (collagen, fibrinogen, fibronectin, laminin, vitronectin, albumin and serum) respond with substrate-dependent modulation of the surface expression of the stimulatory molecule MHC-II and the co-stimulatory molecules CD80 and CD86 and production of the cytokines IL-12p40 and IL-10. Furthermore, the capacity of NOD-DCs to stimulate CD4(+) T-cell proliferation and cytokine production (1-4 and 1FN-gamma) showed substrate-dependent modulation. Specifically, NOD-DCs cultured on vitronectin induced the highest IL-12p40 production, whereas collagen induced the highest IL-10 production. Dendritic cells cultured on collagen, fibrinogen and serum-coated substrates stimulated the highest CD4(+) T-cell proliferation. It was further determined that DCs cultured on vitronectin induced the highest percent population of IL-4-producing T-cells and DCs cultured on a fibronectin-coated substrate induced the highest expression of IFN-gamma in T-cells. Pearson's correlation analysis revealed high correlations between T-cell proliferation and DC expression level of CD80 and T-cell production of IL-4 and DC production of IL-10. This demonstration of substrate-based control of NOD-DC activatory and stimulatory capacity, distinct from nondiabetic B6-DC responses, establishes the field of adhesive modulation of immune cell responses and informs the rational design of biomaterials for patients with type 1 diabetes. Published by Elsevier Ltd. on behalf of Acta Materialia Inc.