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.

不同的免疫调节回路起作用以保持肠道稳态并预防炎症。Galectin-1 (Gal1) 是一种 β-半乳糖苷结合蛋白，通过重新编程先天免疫和适应性免疫来促进体内平衡。在这里，我们确定了由 Gal1 及其糖基化配体驱动的糖基化依赖性“开-关”电路，该电路通过靶向活化的 CD8 ⁺ T 细胞和塑造细胞因子谱来控制肠道免疫病理学。在炎症性肠病 (IBD) 患者中，增强的 Gal1 与核心 2 β6- N-乙酰氨基葡萄糖转移酶1 ( C2GNT1 ) 和 α(2,6)-唾液酸转移酶 1 ( ST6GAL1 ) 的表达失调有关)，负责产生或掩蔽 Gal1 配体的糖基转移酶。缺乏 Gal1 的小鼠表现出对 2,4,6-三硝基苯磺酸的反应加剧的结肠炎和增强的粘膜 CD8 ⁺ T 细胞活化；这种表型通过重组 Gal1 处理得到部分改善。虽然C2gnt1 ^-/-小鼠表现出加重的结肠炎，但St6gal1 ^-/-小鼠表现出减轻的炎症。这些作用与内在 T 细胞糖基化有关。因此，Gal1 及其糖基化配体通过重新校准 T 细胞免疫来维持肠道稳态。