Differential regulation and impact of fucosyltransferase VII and core 2 β1,6‐N‐acetyl‐glycosaminyltransferase for generation of E‐selectin and P‐selectin ligands in murine CD4+ T cells
Differential regulation and impact of fucosyltransferase VII and core 2 β1,6‐N‐acetyl‐glycosaminyltransferase for generation of E‐selectin and P‐selectin ligands in murine CD4+ T cells
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DOI：
10.1111/imm.12011
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发表时间：
2012-12
期刊：
影响因子：
6.4
通讯作者：
M. Schroeter;B. Ratsch;J. Lehmann;R. Baumgrass;A. Hamann;U. Syrbe
中科院分区：
文献类型：
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作者：
M. Schroeter;B. Ratsch;J. Lehmann;R. Baumgrass;A. Hamann;U. Syrbe
E-选择素和 P-选择素的配体（E-lig 和 P-lig）在 CD4+ T 细胞分化为效应 T 细胞时被诱导。糖基转移酶，特别是 α 1,3-岩藻糖基转移酶 VII (FucT-VII) 和核心 2 β1,6-N-乙酰基糖胺基转移酶 I (C2GlcNAcT-I)，对其合成至关重要。我们在这里分析了控制 E-lig、P-lig 和编码 FucT-VII 和 C2GlcNAcT-I 的 mRNA 表达的信号。与之前的报道一致，我们发现 P-lig 表达与 C2GlcNAcT-I 的调节相关，而 E-lig 表达可以在低水平的 C2GlcNAcT-I mRNA 下发生，但需要高水平的 FucT-VII mRNA 表达。有趣的是，这两种酶受到不同信号的调节。环孢菌素 A (CsA) 强烈降低了在允许（T 辅助细胞 1 型）条件下激活诱导的 C2GlcNAcT-I 上调，表明 T 细胞受体依赖性、钙调神经磷酸酶/NFAT 依赖性信号与白介素-12 (IL-12) 介导的信号相结合参与了 C2GlcNAcT-I 的调节。相反，CsA 并未显着抑制 FucT-VII mRNA 的表达。 Interleukin-4 抑制 FucT-VII 的表达，但发现 IL-2 和 IL-7 支持 FucT-VII 和 E-lig 的诱导。 E-选择素、P-选择素及其配体最初似乎具有相当重叠的功能。然而，这些发现揭示了 E-lig 和 P-lig 表达调节的显着差异，分别由 FucT-VII 和 C2GlcNAcT-I 的主导地位决定，以及它们对混杂或稳态细胞因子 (FucT-VII) 信号的依赖，或者在 C2GlcNAcT-I 情况下依赖于与炎症细胞因子结合的强 T 细胞受体信号。
Ligands for E‐selectin and P‐selectin (E‐lig and P‐lig) are induced on CD4+ T cells upon differentiation into effector T cells. Glycosyltransferases, especially α 1,3‐fucosyltransferase VII (FucT‐VII) and core 2 β1,6‐N‐acetyl‐glycosaminyltransferase I (C2GlcNAcT‐I), are critical for their synthesis. We here analysed the signals that control the expression of E‐lig, P‐lig and mRNA coding for FucT‐VII and C2GlcNAcT‐I. In line with previous reports, we found that P‐lig expression correlates with the regulation of C2GlcNAcT‐I, whereas E‐lig expression can occur at low levels of C2GlcNAcT‐I mRNA but requires high FucT‐VII mRNA expression. Interestingly, the two enzymes are regulated by different signals. Activation‐induced C2GlcNAcT‐I up‐regulation under permissive (T helper type 1) conditions was strongly reduced by cyclosporin A (CsA), suggesting the involvement of T‐cell receptor‐dependent, calcineurin/NFAT‐dependent signals in combination with interleukin‐12 (IL‐12) ‐mediated signals in the regulation of C2GlcNAcT‐I. In contrast, expression of FucT‐VII mRNA was not significantly inhibited by CsA. Interleukin‐4 inhibited the expression of FucT‐VII but IL‐2 and IL‐7 were found to support induction of FucT‐VII and E‐lig. E‐selectin, P‐selectin and their ligands initially appeared to have rather overlapping functions. These findings however, unravel striking differences in the regulation of E‐lig and P‐lig expression, dictated by the dominance of FucT‐VII and C2GlcNAcT‐I, respectively, and their dependency on signals from either promiscuous or homeostatic cytokines (FucT‐VII) or a strong T‐cell receptor signal in combination with inflammatory cytokines in case of C2GlcNAcT‐I.