Abstract
Galectin-3 regulates numerous biological processes in the gut. We investigated molecular mechanisms responsible for the Galectin-3-dependent regulation of colon inflammation and evaluated whether Galectin-3 may be used as biomarker for monitoring the progression of ulcerative colitis (UC). The differences in disease progression between dextran sodium sulphate-treated wild type and Galectin-3-deficient mice were investigated and confirmed in clinical settings, in 65 patients suffering from mild, moderate, and severe colitis. During the induction phase of colitis, Galectin-3 promoted interleukin-1β-induced polarization of colonic macrophages towards inflammatory phenotype. In the recovery phase of colitis, Galectin-3 was required for the immunosuppressive function of regulatory dendritic cells (DCs). Regulatory DCs in Galectin-3:Toll-like receptor-4:Kynurenine-dependent manner promoted the expansion of colon-infiltrated T regulatory cells (Tregs) and suppressed Th1 and Th17 cell-driven colon inflammation. Concentration of Galectin-3 in serum and stool samples of UC patients negatively correlated with clinical, endoscopic, and histological parameters of colitis. The cutoff serum values of Galectin-3 that allowed the discrimination of mild from moderate and moderate from severe colitis were 954 pg/mL and 580 pg/mL, respectively. Fecal levels of Galectin-3 higher than 553.44 pg/mL indicated attenuation of UC. In summing up, Galectin-3 regulates the cross-talk between colon-infiltrating DCs and Tregs and represents a new biomarker for monitoring the progression of UC.
Highlights
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) confined to the colon [1].It is characterized by epithelial cell destruction, connective tissue defects, ulceration of the mucosa and continuous or discontinuous mucosal inflammation, which results in remitting and relapsing clinical course [2]
Since concentration of Galectin 3 (Gal-3) in serum and stool samples of UC patients negatively correlated with clinical, endoscopic, and histological parameters of disease severity, we proposed that Gal-3 might serve as a valuable biomarker for monitoring disease progression
In order to determine which molecular and cellular mechanisms were responsible for Gal-3dependent regulation of immune response during inductive and recovery phases of colitis, we compared the differences in clinical course, survival rate, and colon architecture between WT and Gal-3−/− mice during the development and progression of acute dextran sodium sulphate sodium (DSS)-induced colitis
Summary
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) confined to the colon [1]. It is characterized by epithelial cell destruction, connective tissue defects, ulceration of the mucosa and continuous or discontinuous mucosal inflammation, which results in remitting and relapsing clinical course [2]. While endoscopic evaluation of UC progression is the gold standard for the follow-up of UC patients, this diagnostic approach is invasive and time-consuming [3,4]. Measurement of non-invasive inflammation-related biomarkes (C-reactive protein (CRP), fecal calprotectin (FC), and lactoferrin (FL)) in serum and stool samples of UC patients are nowadays used in clinical practice to defer the need for colonoscopic evaluation [5,6]. Keeping in mind that these biomarkers have some limitations related to alimentary ingestion, non-steroidal anti-inflammatory drugs intake and inability of distinguishing inflammation from infection, there is still a need for a new, non-invasive biomarker, which should complement CRP, FC and FL in determination of UC progression [7]
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