Functional Evaluation of Activation-dependent Alterations in the Sialoglycan Composition of T Cells
Functional Evaluation of Activation-dependent Alterations in the Sialoglycan Composition of T Cells
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DOI：
10.1074/jbc.m113.523753
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发表时间：
2014-01-17
影响因子：
4.8
通讯作者：
Takematsu, Hiromu
中科院分区：
文献类型：
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作者：
Naito-Matsui, Yuko;Takada, Shuhei;Takematsu, Hiromu
背景：唾液酸在分子识别中发挥着关键作用。结果：T 细胞激活改变主要唾液酸种类谱，调节 siglec 配体的表达、T 细胞激活本身以及 T 细胞-B 细胞相互作用。结论：唾液酸聚糖谱的这种激活依赖性变化可调节免疫反应。意义：唾液酸聚糖谱的显着变化不仅可以作为细胞标记，还可以反映细胞功能。唾液酸 (Sias) 通常与细胞聚糖的末端缀合，是细胞识别的关键介质。 Sias 是九碳酸性糖，在脊椎动物中，主要种类是 N-乙酰神经氨酸 (Neu5Ac) 和 N-羟乙酰神经氨酸 (Neu5Gc)，其 C5 位点结构不同。之前，我们描述了涉及小鼠 B 细胞中 Neu5Gc 表达调节的正反馈循环。在这种情况下，Neu5Gc 负向调节 B 细胞增殖，并且 Neu5Gc 表达在激活后受到抑制。类似地，静息小鼠 T 细胞主要表达 Neu5Gc，Neu5Ac 在激活后被诱导。在目前的工作中，我们使用各种探针来检查激活的 T 细胞的唾液酸聚糖表达，包括表达的 Sia 种类以及 Sia 与聚糖的连接。 T 细胞激活后，唾液酸聚糖表达从 Neu5Gc 转变为 Neu5Ac，并且连接从 2,6 转变为 2,3。这些变化改变了唾液酸结合免疫球蛋白样凝集素 (siglec) 配体的表达水平。唾液酸粘附素和Siglec-F配体的表达增加，而CD22配体的表达减少。 Neu5Gc 对 T 细胞激活产生负面影响，无论是在增殖反应方面还是在激活标记物表达方面。抑制小鼠 T 细胞和 B 细胞中的 Neu5Gc 表达可阻止 CD22 介导的非特异性 T 细胞-B 细胞相互作用的发展。我们的结果表明，从 Neu5Gc 到 Neu5Ac 的激活依赖性转变以及 2,3 连接替换 2,6 可能在多个水平上调节免疫细胞相互作用。
Background: Sialic acids play key roles in molecular recognition. Results: T-cell activation alters the principal sialic acid species profile, regulating expression of siglec ligands, T-cell activation per se, and T cell-B cell interactions. Conclusion: This activation-dependent change in the sialoglycan profile modulates immune responses. Significance: Pronounced changes in the sialoglycan profile not only serve as cellular markers but also reflect cellular functionality.Sialic acids (Sias) are often conjugated to the termini of cellular glycans and are key mediators of cellular recognition. Sias are nine-carbon acidic sugars, and, in vertebrates, the major species are N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), differing in structure at the C5 position. Previously, we described a positive feedback loop involving regulation of Neu5Gc expression in mouse B cells. In this context, Neu5Gc negatively regulated B-cell proliferation, and Neu5Gc expression was suppressed upon activation. Similarly, resting mouse T cells expressed principally Neu5Gc, and Neu5Ac was induced upon activation. In the present work, we used various probes to examine sialoglycan expression by activated T cells in terms of the Sia species expressed and the linkages of Sias to glycans. Upon T-cell activation, sialoglycan expression shifted from Neu5Gc to Neu5Ac, and the linkage shifted from 2,6 to 2,3. These changes altered the expression levels of sialic acid-binding immunoglobulin-like lectin (siglec) ligands. Expression of sialoadhesin and Siglec-F ligands increased, and that of CD22 ligands decreased. Neu5Gc exerted a negative effect on T-cell activation, both in terms of the proliferative response and in the context of activation marker expression. Suppression of Neu5Gc expression in mouse T and B cells prevented the development of nonspecific CD22-mediated T cell-B cell interactions. Our results suggest that an activation-dependent shift from Neu5Gc to Neu5Ac and replacement of 2,6 by 2,3 linkages may regulate immune cell interactions at several levels.