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Abstract：
New strategies for immune modulation have shown real promise in regenerative medicine as well as the fight against autoimmune diseases, allergies, and cancer. Dendritic cells (DCs) are gatekeepers of the immune system and their ability in shaping the adaptive immune responses makes DCs ideal targets for immune modulation. Carbohydrates are abundant in different biological systems and are known to modulate DC phenotype and function. However, how simple monosaccharides instruct DC function is less well understood. In this study, we used a combinatorial array of immobilized monosaccharides to investigate how they modulate DC phenotype and function and crucially the impact of such changes on downstream adaptive immune responses. Our data show that a selection of monosaccharides significantly suppress lipopolysaccharide-induced DC activation as evidenced by a reduction in CD40 expression, IL-12 production, and indoleamine 2,3-dioxygenase activity, while inducing a significant increase in IL-10 production. These changes are indicative of the induction of an anti-inflammatory or regulatory phenotype in DCs, which was further confirmed in DC-T cell co-cultures where DCs cultured on the \'regulatory\' monosaccharide-coated surfaces were shown to induce naïve T cell polarization toward regulatory phenotype. Our data also highlighted a selection of monosaccharides that are able to promote mixed Treg and Th17 cell differentiation, a T cell phenotype expected to be highly immune suppressive. These data show the potential immunomodulatory effects of immobilized monosaccharides in priming DCs and skewing T cell differentiation toward an immune-regulatory phenotype. The ability to fine-tune immune responses using these simple carbohydrate combinations (e.g. as coatings for existing materials) can be utilized as novel tools for immune modulation with potential applications in regenerative medicine, implantable medical devices, and wound healing where reduction of inflammatory responses and maintaining immune homeostasis are desirable.
摘要：
免疫调节的新策略在再生医学以及对抗自身免疫性疾病方面显示出真正的希望，过敏,和癌症。树突状细胞（DC）是免疫系统的看门人，它们形成适应性免疫反应的能力使DC成为免疫调节的理想目标。碳水化合物在不同的生物系统中是丰富的,并且已知调节DC表型和功能。然而,简单的单糖如何指导DC功能还不太清楚。在这项研究中,我们使用固定化单糖的组合阵列来研究它们如何调节DC表型和功能,以及这些变化对下游适应性免疫应答的影响。我们的数据显示，单糖的选择显着抑制脂多糖诱导的DC活化，如CD40表达的减少所证明，IL-12生产，和吲哚胺2,3-双加氧酶活性，同时诱导IL-10产生的显著增加。这些变化表明在DC中诱导了抗炎或调节表型，这在DC-T细胞共培养中得到了进一步证实，其中在调节性单糖包被表面上培养的DC显示诱导初始T细胞向调节性表型极化。我们的数据还强调了能够促进混合Treg和Th17细胞分化的单糖的选择，T细胞表型预期是高度免疫抑制的。这些数据显示了固定化单糖在引发DC和使T细胞分化偏向免疫调节表型中的潜在免疫调节作用。使用这些简单的碳水化合物组合（例如作为现有材料的涂层）微调免疫反应的能力可以用作免疫调节的新工具，在再生医学中具有潜在的应用。植入式医疗器械,和伤口愈合，其中减少炎症反应和维持免疫稳态是可取的。
