Hydrogel presents as foreign material to the host and participates in immune responses, which skew the biofunctions of immunologic loads (antigen and adjuvants) during in situ DC priming. This study aims to investigate the effect of the hydrogel made from different polysaccharides on macrophage (RAW264.7) activation and DC (JAWSII) modulation. We adopted polysaccharides of different sugar chemistry to fabricate hydrogels. Hyaluronate (HA), glycol chitosan (GC) and dextran (DX) were functionalized with vinyl sulfone and chemically cross-linked with dithiothreitol via thiol-click chemistry. We found that HA reduced macrophage adhesion and activation on the hydrogel surface. GC and DX promoted M1 polarization in terms of higher CCR7 expression and TNF-α, IL-6 production. In terms of DC engagement, GC promoted antigen uptake by JAWSII and all hydrogels promoted antigen presentation on MHC-I molecules. GC and DX favoured the generation of immunogenic DC while accommodating immunostimulatory functions of IFN-γ and polyI:C or LPS during co-incubation. Particularly, the co-incubation of IP with GC promoted CCR7 expression on JAWSII. Conversely, HA was more appropriate for the construction of a tolerogenic DC priming platform. We observed that HA did not induce co-stimulatory markers expression on DC but suppressed the action of LPS in inducing TNF-α generation. Moreover, when immunosuppressive cytokines, IL-10 and TGF-β were added, cytokines’ immunosuppressive action was amplified by hydrogel bedding, HA, GC and to a less extent DX in suppressing LPS-induced IL-6 generation from JAWSII. We concluded that HA is preferable for tolerogenic DC development while minimizing the macrophage response in conferring foreign body response, whereas DX and GC are more appropriate for immunogenic DC development. This study demonstrates the potential of polysaccharides in conferring in situ DC priming together with antigen and adjuvant loads while addressing the tradeoff between the foreign body responses and DC engagement by selecting appropriate polysaccharides for the hydrogel platform construction.

中文翻译：

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多糖基水凝胶对抗原呈递细胞系对免疫调节剂反应的影响

水凝胶作为外来物质呈现给宿主并参与免疫反应，这会在原位DC 引发期间扭曲免疫负荷（抗原和佐剂）的生物功能。本研究旨在研究由不同多糖制成的水凝胶对巨噬细胞 (RAW264.7) 激活和 DC (JAWSII) 调节的影响。我们采用不同糖化学的多糖来制造水凝胶。透明质酸 (HA)、乙二醇壳聚糖 (GC) 和葡聚糖 (DX) 被乙烯基砜官能化，并通过二硫苏糖醇化学交联硫醇点击化学。我们发现 HA 减少了巨噬细胞在水凝胶表面的粘附和活化。就更高的 CCR7 表达和 TNF-α、IL-6 产生而言，GC 和 DX 促进了 M1 极化。在 DC 参与方面，GC 促进了 JAWSII 对抗原的吸收，所有水凝胶都促进了 MHC-I 分子上的抗原呈递。GC 和 DX 有利于产生免疫原性 DC，同时在共孵育过程中调节 IFN-γ 和 polyI:C 或 LPS 的免疫刺激功能。特别是，IP 与 GC 的共同孵育促进了 JAWSII 上 CCR7 的表达。相反，HA更适合构建耐受性DC启动平台。我们观察到 HA 不诱导 DC 上的共刺激标志物表达，但抑制 LPS 在诱导 TNF-α 生成中的作用。此外，当免疫抑制细胞因子，添加了 IL-10 和 TGF-β，细胞因子的免疫抑制作用通过水凝胶床上用品、HA、GC 和较小程度的 DX 放大，以抑制 LPS 诱导的 JAWSII IL-6 生成。我们得出的结论是 HA 更适合于致耐受性 DC 的发展，同时最大限度地减少巨噬细胞在赋予异物反应方面的反应，而 DX 和 GC 更适合于免疫原性 DC 的发展。这项研究证明了多糖在赋予 而 DX 和 GC 更适合免疫原性 DC 发展。这项研究证明了多糖在赋予 而 DX 和 GC 更适合免疫原性 DC 发展。这项研究证明了多糖在赋予原位DC 引发与抗原和佐剂负载一起，同时通过为水凝胶平台构建选择合适的多糖来解决异物反应和 DC 接合之间的权衡。