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

Rodrigo Papa-Gobbi, Cecilia I. Muglia, Andrés Rocca, Renata Curciarello, Alicia M. Sambuelli, Martín Yantorno, Gustavo Correa, Luciano G. Morosi, Antonio Di Sabatino, Paolo Biancheri, Thomas T. MacDonald, Marta A. Toscano, Karina V. Mariño, Gabriel A. Rabinovich, Guillermo H. Docena

Research output: Contribution to journalArticlepeer-review

Abstract

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 induction of 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 surgical specimens from control patients (n = 52) and patients with active or inactive IBD (n = 97) were studied. Gal-1 expression was studied by RT-qPCR, immunoblotting, ELISA and immunohistochemistry. Gal-1-specific ligands and Gal-1-induced apoptosis of lamina propria (LP) T-cells were determined by TUNEL and flow cytometry. We found a transient expression of asialo 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 enzyme responsible 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-cells isolated 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 LP T-cell survival in IBD patients.

Original languageEnglish
JournalApoptosis
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • Crohn Disease
  • Galectin-1
  • Gut
  • Inflammation
  • Inflammatory bowel disease
  • O-glycosylation
  • T-cells
  • Ulcerative Colitis

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

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