ABSTRACT
Diverse immunoregulatory circuits operate to preserve intestinal homeostasis and prevent inflammation. Galectin-1 (Gal1), a ß-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 ß6-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.
ABSTRACT
The gold standard to quantify Crohn's disease activity is still not defined and a world consensus to unify criteria is necessary. Criticism has been directed towards every existing indexes. We summarize some of the currently used criteria for the assessment of disease activity, point out the controversies and issues that will need further investigations, and discuss their usefulness based on our experience.
Subject(s)
Crohn Disease/diagnosis , Severity of Illness Index , Biomarkers/analysis , HumansABSTRACT
The gold standard to quantify Crohns disease activity is still not defined and a world consensus to unify criteria is necessary. Criticism has been directed towards every existing indexes. We summarize some of the currently used criteria for the assessment of disease activity, point out the controversies and issues that will need further investigations, and discuss their usefulness based on our experience.
ABSTRACT
No se ha definido aún un método gold standard para cuantificar la actividad de la enfermedad de Crohn, por lo que es necesario unificar criterios a través de un consenso mundial. Cada uno de los índices descriptos para tal fin han sido criticados. En el presente trabajo realizamos una revisión de los criterios actualmente utilizados para evaluar la actividad de la enfermedad, destacamos las controversias existentes y los temas que aún requieren ser investigados, y analizamos su utilidad en base a nuestra experiencia. (AU)
Subject(s)
Humans , Crohn Disease/diagnosis , Severity of Illness Index , Biomarkers/analysisABSTRACT
No se ha definido aún un método gold standard para cuantificar la actividad de la enfermedad de Crohn, por lo que es necesario unificar criterios a través de un consenso mundial. Cada uno de los índices descriptos para tal fin han sido criticados. En el presente trabajo realizamos una revisión de los criterios actualmente utilizados para evaluar la actividad de la enfermedad, destacamos las controversias existentes y los temas que aún requieren ser investigados, y analizamos su utilidad en base a nuestra experiencia.
The gold standard to quantify Crohn's disease activity is still not defined and a world consensus to unify criteria is necessary. Criticism has been directed towards every existing indexes. We summarize some of the currently used criteria for the assessment of disease activity, point out the controversies and issues that will need further investigations, and discuss their usefulness based on our experience.