Articulo
Control of intestinal inflammation by glycosylation-dependent lectin-driven immunoregulatory circuits
Registro en:
issn:2375-2548
Autor
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.
Institución
Resumen
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<sup>-/-</sup> mice exhibited aggravated colitis, St6gal1<sup>-/-</sup> 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