期刊
SCIENCE ADVANCES
卷 7, 期 25, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abf8630
关键词
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资金
- Kenneth Rainin Foundation
- Crohn and Colitis Foundation of America [IBD-0378]
- CONICET [PIP 2013-2015-041]
- Argentinean Agency for Promotion of Science and Technology [PICT 2012-0555, PICT 2014-3687]
- Bunge & Born Foundation
- Baron Foundation
- Lounsbery Foundation
- Sales Foundation
The study reveals a glycosylation-dependent on-off circuit controlled by Galectin-1 (Gal1) and its glycosylated ligands which target activated CD8(+) T cells and shape cytokine profile to maintain intestinal homeostasis. In patients with inflammatory bowel disease, increased Gal1 is associated with dysregulated expression of glycosyltransferases C2GNT1 and ST6GAL1. This provides insights into the role of Gal1 and its glycosylated ligands in recalibrating T cell immunity to preserve intestinal homeostasis.
Diverse immunoregulatory circuits operate to preserve intestinal homeostasis and prevent inflammation. Galectin-1 (Gal1), a beta-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 2.6-N-acetylglucosaminyltransferase 1 (C2GNT1) and alpha(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.
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