Developing immune-regulatory materials using immobilized monosaccharides with immune-instructive properties.
Developing immune-regulatory materials using immobilized monosaccharides with immune-instructive properties.
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DOI：
10.1016/j.mtbio.2020.100080
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发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Ghaemmaghami AM
中科院分区：
文献类型：
--
作者：
Alobaid MA;Richards SJ;Alexander MR;Gibson MI;Ghaemmaghami AM
免疫调节的新策略在再生医学以及对抗自身免疫性疾病、过敏和癌症方面显示出真实的前景。树突状细胞（DC）是免疫系统的守门人，其形成适应性免疫应答的能力使DC成为免疫调节的理想靶点。碳水化合物在不同的生物系统中是丰富的，并且已知其调节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，我们使用了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。我们的数据表明，单糖的选择显着抑制脂多糖诱导的DC活化，证明了在CD 40表达，IL-12的生产，和吲哚胺2，3-双加氧酶活性的减少，同时诱导IL-10的生产显着增加。这些变化表明DC中抗炎或调节表型的诱导，这在DC-T细胞共培养物中得到进一步证实，其中在“调节性”单糖包被的表面上培养的DC显示诱导幼稚T细胞向调节表型极化。我们的数据还强调了能够促进混合Treg和Th 17细胞分化的单糖的选择，这是一种预期具有高度免疫抑制性的T细胞表型。这些数据显示了固定化单糖在引发DC和使T细胞分化向免疫调节表型倾斜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）微调免疫应答的能力可以用作免疫调节的新工具，其在再生医学、可植入医疗装置和伤口愈合中具有潜在的应用，其中期望减少炎症应答和维持免疫稳态。
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.
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影响因子：
15.3
作者：
Geijtenbeek, TBH;van Vliet, SJ;Koppel, EA;Sanchez-Hernandez, M;Vandenbroucke-Grauls, CMJE;Appelmelk, B;van Kooyk, Y
通讯作者：
van Kooyk, Y
影响因子：
44.1
作者：
Hwang, SL;Chung, NPY;Lin, CLS
通讯作者：
Lin, CLS
影响因子：
--
作者：
Hudak JE;Bertozzi CR
通讯作者：
Bertozzi CR
影响因子：
16.6
作者：
Downs-Canner S;Berkey S;Delgoffe GM;Edwards RP;Curiel T;Odunsi K;Bartlett DL;Obermajer N
通讯作者：
Obermajer N
影响因子：
7.2
作者：
Chellappa, Stalin;Hugenschmidt, Harald;Aandahl, Einar M.
通讯作者：
Aandahl, Einar M.