Volarevic, Vladislav; Zdravkovic, Natasa; Harrell, Carl Randall; Arsenijevic, Nebojsa; Fellabaum, Crissy; Djonov, Valentin; Lukic, Miodrag L; Simovic Markovic, Bojana (2019). Galectin-3 Regulates Indoleamine-2,3-dioxygenase-Dependent Cross-Talk between Colon-Infiltrating Dendritic Cells and T Regulatory Cells and May Represent a Valuable Biomarker for Monitoring the Progression of Ulcerative Colitis. Cells, 8(7) MDPI 10.3390/cells8070709
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy 04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Topographical and Clinical Anatomy |
UniBE Contributor: |
Djonov, Valentin Georgiev |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2073-4409 |
Publisher: |
MDPI |
Language: |
English |
Submitter: |
David Christian Haberthür |
Date Deposited: |
30 Dec 2020 10:34 |
Last Modified: |
05 Dec 2022 15:42 |
Publisher DOI: |
10.3390/cells8070709 |
PubMed ID: |
31336879 |
Uncontrolled Keywords: |
Galectin-3 Kynurenine T regulatory cells Toll-like receptor-4 biomarker dendritic cells immunomodulation ulcerative colitis |
BORIS DOI: |
10.48350/149212 |
URI: |
https://boris.unibe.ch/id/eprint/149212 |
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