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

• Autores: Morosi, Luciano Gastón; Cutine, Anabela M.; Cagnoni, Alejandro J.; Manselle Cocco, Montana N.; Merlo, Joaquín P.; Morales, Rosa M.; May, María; Pérez Sáez, Juan M.; Girotti, María Romina; Méndez Huergo, Santiago P.; Pucci, Betiana; Gil, Aníbal H.; Huernos, Sergio P.; Docena, Guillermo Horacio; Sambuelli, Alicia M.; Toscano, Marta A.; Rabinovich, Gabriel A.; Mariño, Karina V.
• Año de publicación: 2021
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Medicina; Ciencias Exactas; intestinal homeostasis; proteins; inflammatory bowel disease (IBD)
• Institución: Universidad Nacional de La Plata

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.
Facultad de Ciencias Exactas
Instituto de Estudios Inmunológicos y Fisiopatológicos