| First Author | Morosi LG | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 25 | PubMed ID | 34144987 |
| Mgi Jnum | J:338681 | Mgi Id | MGI:6814430 |
| Doi | 10.1126/sciadv.abf8630 | Citation | Morosi LG, et al. (2021) Control of intestinal inflammation by glycosylation-dependent lectin-driven immunoregulatory circuits. Sci Adv 7(25) |
| abstractText | 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 beta6-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. |
