Spatiotemporal regulation of galectin-1-induced T-cell death in lamina propria from Crohn’s disease and ulcerative colitis patients

PAPA-GOBBI, RODRIGO; MUGLIA, CECILIA I.; ROCCA, ANDRÉS; CURCIARELLO, RENATA; SAMBUELLI, ALICIA M.; YANTORNO, MARTÍN; CORREA, GUSTAVO; MOROSI, LUCIANO G.; DI SABATINO, ANTONIO; BIANCHERI, PAOLO; MACDONALD, THOMAS T.; TOSCANO, MARTA A.; MARIÑO, KARINA V.; RABINOVICH, GABRIEL A.; DOCENA, GUILLERMO H.

APOPTOSIS

SPRINGER

Lugar: Berlin; Año: 2021

1360-8185

Inflammatory bowel disease (IBD), including Crohn?s disease (CD) and ulcerative colitis (UC), is characterized by chronic,relapsing intestinal inflammation. Galectin-1 (Gal-1) is an endogenous lectin with key pro-resolving roles, including inductionof T-cell apoptosis and secretion of immunosuppressive cytokines. Despite considerable progress, the relevance of Gal-1-induced T-cell death in inflamed tissue from human IBD patients has not been ascertained. Intestinal biopsies and surgicalspecimens from control patients (n = 52) and patients with active or inactive IBD (n = 97) were studied. Gal-1 expressionwas studied by RT-qPCR, immunoblotting, ELISA and immunohistochemistry. Gal-1-specific ligands and Gal-1-inducedapoptosis of lamina propria (LP) T-cells were determined by TUNEL and flow cytometry. We found a transient expression ofasialo core 1-O-glycans in LP T-cells from inflamed areas (p < 0.05) as revealed by flow cytometry using peanut agglutinin(PNA) binding and assessing dysregulation of the core-2 β 1-6-N-acetylglucosaminyltransferase 1 (C2GNT1), an enzymeresponsible for elongation of core 2 O-glycans. Consequently, Gal-1 binding was attenuated in CD3+CD4+ and CD3+CD8+LP T-cells isolated from inflamed sites (p < 0.05). Incubation with recombinant Gal-1 induced apoptosis of LP CD3+T-cellsisolated from control subjects and non-inflamed areas of IBD patients (p < 0.05), but not from inflamed areas. In conclusion,our findings showed that transient regulation of the O-glycan profile during inflammation modulates Gal-1 binding and LPT-cell survival in IBD patients.