Science子刊:Gal1及其糖基化配体调节CD8+ T细胞以维持肠道稳态
创作:圆滑的铁勺 审核:aluba 07月13日
  • IBD患者结肠炎症部位的Gal1上调且特定糖基转移酶表达失调,C2GNT1(促进Gal1结合)下调,ST6GAL1(抑制Gal1结合)上调;
  • 缺失Gal1可恶化TNBS诱导的小鼠结肠炎,增加肠系膜淋巴结中的CD4+ 及CD8+ T细胞,而补充重组Gal1可部分缓解;
  • 缺失C2GNT1可恶化小鼠结肠炎,而缺失ST6GAL1则可缓解小鼠结肠炎;
  • TNBS诱导的结肠炎可增加结肠固有层CD8+ T细胞的Gal1与其糖基化配体的结合,提示Gal1及其糖基化配体通过作用于CD8+ T细胞调控肠道炎症。
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半乳凝素-1(Gal1)是一种β-半乳糖苷结合蛋白,通过重塑先天性及适应性免疫促进稳态。Science Advances上发表的一项最新研究,揭示了Gal1及其糖基化配体(后者受特定糖基转移酶的调控)通过影响CD8+ T细胞,以调节肠道免疫稳态的机制。缺失Gal1可恶化小鼠结肠炎,补充重组Gal1可缓解,而在IBD患者的炎症结肠部位的Gal1表达上调。
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Science Advances [IF:14.136]

Control of intestinal inflammation by glycosylation-dependent lectin-driven immunoregulatory circuits

糖基化依赖性的凝集素驱动的免疫调节回路控制肠道炎症

10.1126/sciadv.abf8630

06-18, Article

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Diverse immunoregulatory circuits operate to preserve intestinal homeostasis and prevent inflammation. Galectin-1 (Gal1), a β-galactoside–binding protein, promotes homeostasis by reprogramming innate and adaptive immunity. Here, we identify a glycosylation-dependent “on-off” circuit driven by Gal1 and its glycosylated ligands that controls intestinal immunopathology by targeting activated CD8+ T cells and shaping the cytokine profile. In patients with inflammatory bowel disease (IBD), augmented Gal1 was associated with dysregulated expression of core 2 β6-N-acetylglucosaminyltransferase 1 (C2GNT1) and α(2,6)-sialyltransferase 1 (ST6GAL1), glycosyltransferases responsible for creating or masking Gal1 ligands. Mice lacking Gal1 exhibited exacerbated colitis and augmented mucosal CD8+ T cell activation in response to 2,4,6-trinitrobenzenesulfonic acid; this phenotype was partially ameliorated by treatment with recombinant Gal1. While C2gnt1−/− mice exhibited aggravated colitis, St6gal1−/− mice showed attenuated inflammation. These effects were associated with intrinsic T cell glycosylation. Thus, Gal1 and its glycosylated ligands act to preserve intestinal homeostasis by recalibrating T cell immunity.

First Authors:
Luciano G Morosi

Correspondence Authors:
Gabriel A Rabinovich,Karina V Mariño

All Authors:
Luciano G Morosi,Anabela M Cutine,Alejandro J Cagnoni,Montana N Manselle-Cocco,Diego O Croci,Joaquín P Merlo,Rosa M Morales,María May,Juan M Pérez-Sáez,María R Girotti,Santiago P Méndez-Huergo,Betiana Pucci,Aníbal H Gil,Sergio P Huernos,Guillermo H Docena,Alicia M Sambuelli,Marta A Toscano,Gabriel A Rabinovich,Karina V Mariño

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