Galectin-3 Modulates Experimental Colitis

Lippert, Elisabeth; Stieber-Gunckel, Manuela; Dunger, Nadja; Falk, Werner; Obermeier, Florian; Kunst, C

doi:10.1159/000431312

Cited by 13 publications

(16 citation statements)

References 42 publications

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“…Galectin-3 behaves mainly as a proinflammatory protein, and studies using null mutant mice support a rate-limiting role in chronic inflammation with fibrosis in many tissues. In a mice colitis experimental model, intraperitoneally administrated galectin-3 reduced inflammation [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Studies on Galectin Expression in Colectomised Patients with Ulcerative Colitis

Block

Mölne

Leffler

et al. 2016

BioMed Research International

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Introduction. The aetiology and pathogenesis of ulcerative colitis (UC) are essentially unknown. Galectins are carbohydrate-binding lectins involved in a large number of physiological and pathophysiological processes. Little is known about the role of galectins in human UC. In this immunohistochemical exploratory study, both epithelial and inflammatory cell galectin expression were studied in patients with a thoroughly documented clinical history and were correlated with inflammatory activity. Material and Methods. Surgical whole intestinal wall colon specimens from UC patients (n = 22) and controls (n = 10) were studied. Clinical history, pharmacological treatment, and modified Mayo-score were recorded. Tissue inflammation was graded, and sections were stained with antibodies recognizing galectin-1, galectin-2, galectin-3, and galectin-4. Results. Galectin-1 was undetectable in normal and UC colonic epithelium, while galectin-2, galectin-3, and galectin-4 were strongly expressed. A tendency towards diminished epithelial expression with increased inflammatory grade for galectin-2, galectin-3, and galectin-4 was also found. In the inflammatory cells, a strong expression of galectin-2 and a weak expression of galectin-3 were seen. No clear-cut correlation between epithelial galectin expression and severity of the disease was found. Conclusion. Galectin expression in patients with UC seems to be more dependent on disease focality and individual variation than on degree of tissue inflammation.

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical Studies on Galectin Expression in Colectomised Patients with Ulcerative Colitis

Block

Mölne

Leffler

et al. 2016

BioMed Research International

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“…Notably, in IBD patients Gal-3 levels are reduced in active inflamed areas, probably aimed at limiting the inflammatory process and restoring mucosal homeostasis ( 77 , 87 – 89 ). In contrast, a protective role for this lectin was suggested in both the DSS-induced and the T-cell transfer colitis models, through suppression of IL-6 production by colonic LP fibroblasts or by induction of Foxp3 + Tregs ( 90 , 91 ). These discrepancies could be explained not only by differences in experimental models ( 92 ), but also by dissimilar roles of endogenous versus exogenous Gal-3 during different stages of the inflammatory response ( 16 , 29 ).…”

Section: Galectins In Intestinal Inflammatory Diseasesmentioning

confidence: 99%

Galectins in Intestinal Inflammation: Galectin-1 Expression Delineates Response to Treatment in Celiac Disease Patients

et al. 2018

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Galectins, a family of animal lectins characterized by their affinity for N-acetyllactosamine-enriched glycoconjugates, modulate several immune cell processes shaping the course of innate and adaptive immune responses. Through interaction with a wide range of glycosylated receptors bearing complex branched N-glycans and core 2-O-glycans, these endogenous lectins trigger distinct signaling programs thereby controling immune cell activation, differentiation, recruitment and survival. Given the unique features of mucosal inflammation and the differential expression of galectins throughout the gastrointestinal tract, we discuss here key findings on the role of galectins in intestinal inflammation, particularly Crohn’s disease, ulcerative colitis, and celiac disease (CeD) patients, as well as in murine models resembling these inflammatory conditions. In addition, we present new data highlighting the regulated expression of galectin-1 (Gal-1), a proto-type member of the galectin family, during intestinal inflammation in untreated and treated CeD patients. Our results unveil a substantial upregulation of Gal-1 accompanying the anti-inflammatory and tolerogenic response associated with gluten-free diet in CeD patients, suggesting a major role of this lectin in favoring resolution of inflammation and restoration of mucosal homeostasis. Thus, a coordinated network of galectins and their glycosylated ligands, exerting either anti-inflammatory or proinflammatory responses, may influence the interplay between intestinal epithelial cells and the highly specialized gut immune system in physiologic and pathologic settings.

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“…Concentration of Gal-3 was significantly increased in serum samples of UC patients compared to healthy controls [8]. Interestingly, lack of Gal-3 expression showed different effects on the effector function of colon-infiltrated macrophages and T cells [9,10,11]. Gal-3 is highly expressed on colonic macrophages of UC patients and its deficiency inhibits activation of NLRP3 inflammasome and production of inflammatory cytokines in these cells, resulting in attenuation of acute colitis [9].…”

Section: Introductionmentioning

confidence: 99%

“…Gal-3 is highly expressed on colonic macrophages of UC patients and its deficiency inhibits activation of NLRP3 inflammasome and production of inflammatory cytokines in these cells, resulting in attenuation of acute colitis [9]. On contrary, after the treatment with recombinant Gal-3, T cells of UC patients developed immunosuppressive phenotype and are not able to optimally proliferate [10,11,12]. Additionally, adoptive transfer of Gal-3-primed T cells significantly attenuated chronic dextran sodium sulphate sodium (DSS)-induced colitis in mice [10,11,12].…”

Section: Introductionmentioning

confidence: 99%

“…On contrary, after the treatment with recombinant Gal-3, T cells of UC patients developed immunosuppressive phenotype and are not able to optimally proliferate [10,11,12]. Additionally, adoptive transfer of Gal-3-primed T cells significantly attenuated chronic dextran sodium sulphate sodium (DSS)-induced colitis in mice [10,11,12]. Keeping in mind that macrophages play important roles in the induction phase of colitis, while T cells are the most important effector immune cells for progression of colon inflammation, herewith, by using clinical data and complementary in vitro and in vivo approaches, we tried to delineate molecular mechanisms, which are responsible for Gal-3-dependent regulation of immune response in the inflamed gut and to determine whether Gal-3 may be used as a valuable biomarker for monitoring UC progression.…”

Section: Introductionmentioning

confidence: 99%

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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

Volarević

Zdravković

Harrell³

et al. 2019

Cells

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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.

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Galectin-3 Modulates Experimental Colitis

Cited by 13 publications

References 42 publications

Immunohistochemical Studies on Galectin Expression in Colectomised Patients with Ulcerative Colitis

Immunohistochemical Studies on Galectin Expression in Colectomised Patients with Ulcerative Colitis

Galectins in Intestinal Inflammation: Galectin-1 Expression Delineates Response to Treatment in Celiac Disease Patients

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

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