Dendritic cells: a spot on sialic Acid.
Dendritic cells: a spot on sialic Acid.
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DOI：
10.3389/fimmu.2013.00491
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发表时间：
2013-12-27
影响因子：
7.3
通讯作者：
Videira PA
中科院分区：
文献类型：
--
作者：
Crespo HJ;Lau JT;Videira PA
修饰细胞表面的多糖和分泌的蛋白质和脂类占据了发生关键的宿主-宿主和宿主-病原体相互作用的连接点。糖链表位在细胞-细胞和细胞-病原体黏附事件中的作用已经被证实，细胞表面的糖链结构在刺激和炎症信号的响应下迅速改变。尽管人们普遍认为葡聚糖与免疫密切相关，但关于葡聚糖及其变化对整体免疫反应的确切作用仍未明确。唾液酸是一种独特的糖，通常占据糖链的末端位置，可以被外部因素，如病原体，或特定的生理细胞事件所修饰。在细胞表面，唾液酸修饰的结构形成了许多已知参与细胞黏附和细胞转运的受体的关键基本决定因素，例如选择素和Siglec家族的碳水化合物识别受体。树突状细胞(DC)主导着从先天免疫到获得性免疫的转变，在抗原的筛选、摄取和递呈给淋巴细胞，最终触发获得性免疫反应方面，没有其他细胞具有这样的相关作用。有趣的是，唾液酸修饰的结构参与了所有DC功能，如抗原摄取、DC迁移和启动T细胞反应的能力。唾液酸含量随着DC的分化和激活而变化，虽然这些变化尚未完全了解，但这些变化在DC功能中具有重要意义。本文综述了DC表面唾液酸的发育调节，以及DC表面唾液酸如何通过改变抗原吞噬、病原体和肿瘤细胞识别、细胞募集和T细胞启动能力来影响免疫关键的DC功能。现有证据表明，DC表面唾液酸化有可能成为改进和多样化DC治疗的治疗靶点。
Glycans decorating cell surface and secreted proteins and lipids occupy the juncture where critical host–host and host-pathogen interactions occur. The role of glycan epitopes in cell–cell and cell-pathogen adhesive events is already well-established, and cell surface glycan structures change rapidly in response to stimulus and inflammatory cues. Despite the wide acceptance that glycans are centrally implicated in immunity, exactly how glycans and their changes contribute to the overall immune response remains poorly defined. Sialic acids are unique sugars that usually occupy the terminal position of the glycan chains and may be modified by external factors, such as pathogens, or upon specific physiological cellular events. At cell surface, sialic acid-modified structures form the key fundamental determinants for a number of receptors with known involvement in cellular adhesiveness and cell trafficking, such as the Selectins and the Siglec families of carbohydrate recognizing receptors. Dendritic cells (DCs) preside over the transition from innate to the adaptive immune repertoires, and no other cell has such relevant role in antigen screening, uptake, and its presentation to lymphocytes, ultimately triggering the adaptive immune response. Interestingly, sialic acid-modified structures are involved in all DC functions, such as antigen uptake, DC migration, and capacity to prime T cell responses. Sialic acid content changes along DC differentiation and activation and, while, not yet fully understood, these changes have important implications in DC functions. This review focuses on the developmental regulation of DC surface sialic acids and how manipulation of DC surface sialic acids can affect immune-critical DC functions by altering antigen endocytosis, pathogen and tumor cell recognition, cell recruitment, and capacity for T cell priming. The existing evidence points to a potential of DC surface sialylation as a therapeutic target to improve and diversify DC-based therapies.