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.

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)

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:

31 Dec 2020 13:22

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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