Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death
Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death
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DOI：
10.1038/ni1482
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发表时间：
2007-08-01
影响因子：
30.5
通讯作者：
Rabinovich, Gabriel A.
中科院分区：
文献类型：
--
作者：
Toscano, Marta A.;Bianco, German A.;Rabinovich, Gabriel A.
受调节的糖基化通过产生或掩蔽内源性凝集素的配体来控制T细胞过程，包括活化、分化和归巢。在这里，我们表明，刺激促进T辅助细胞1型（T（H）1），T（H）2或白细胞介素17产生的T辅助细胞（T-H-17）分化可以差异调节T辅助细胞的糖基化模式，并调节其对半乳糖凝集素-1，一种具有抗炎活性的聚糖结合蛋白的敏感性。虽然T（H）1和T-H-17分化的细胞表达了半乳糖凝集素-1诱导细胞死亡的关键细胞表面聚糖的所有组成部分，但T（H）2细胞通过细胞表面糖蛋白的差异唾液酸化而免受半乳糖凝集素-1的影响。与这些发现一致，半乳糖凝集素-1缺陷小鼠产生了更大的T（H）1和T-H-17反应，并增强了对自身免疫性神经炎症的易感性。我们的研究结果确定了T辅助细胞的差异糖基化，细胞死亡的易感性和炎症反应的终止之间的分子联系。
Regulated glycosylation controls T cell processes, including activation, differentiation and homing by creating or masking ligands for endogenous lectins. Here we show that stimuli promoting T helper type 1 (T(H)1), T(H)2 or interleukin 17-producing T helper (T-H-17) differentiation can differentially regulate the glycosylation pattern of T helper cells and modulate their susceptibility to galectin-1, a glycan-binding protein with anti-inflammatory activity. Although T(H)1- and T-H-17-differentiated cells expressed the repertoire of cell surface glycans critical for galectin-1-induced cell death, T(H)2 cells were protected from galectin-1 through differential sialylation of cell surface glycoproteins. Consistent with those findings, galectin-1-deficient mice developed greater T(H)1 and T-H-17 responses and enhanced susceptibility to autoimmune neuroinflammation. Our findings identify a molecular link among differential glycosylation of T helper cells, susceptibility to cell death and termination of the inflammatory response.