Galectin-1: A Jack-of-All-Trades in the Resolution of Acute and Chronic Inflammation

Sundblad, Victoria; Morosi, Luciano Gastón; Geffner, Jorge; Rabinovich, Gabriel A.

doi:10.4049/jimmunol.1701172

Cited by 152 publications

(140 citation statements)

References 139 publications

(196 reference statements)

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“…The gene expression profiling that we performed on the Mdr2-KO livers at the precancerous stages of liver disease revealed aberrant expression of several immune and inflammatory regulatory genes that have an important role in hepatocarcinogenesis, including up-regulation of Lgals1, which encodes galectin-1 (Gal1) (3). Gal1 is widely expressed in epithelial and immune cells and acts both extracellularly and intracellularly, modulating innate and adaptive immune responses and acting as a homeostatic agent (4). It promotes apoptosis of activated CD8 T cells, T helper (T h )1, and T h 17 cells; suppresses the secretion of proinflammatory IL-2 and IFN-g; and favors the secretion of anti-inflammatory IL-10 and TGF-b1 (5)(6)(7).…”

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confidence: 99%

Lack of galectin‐1 exacerbates chronic hepatitis, liver fibrosis, and carcinogenesis in murine hepatocellular carcinoma model

et al. 2019

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Chronic liver inflammation (CLI) is a risk factor for development of hepatocellular carcinoma (HCC). Galectin‐1 (Gal1) is involved in the regulation of inflammation, angiogenesis, and tumorigenesis, exhibiting multiple anti‐inflammatory and protumorigenic activities. We aimed to explore its regulatory role in CLI and HCC progression using an established model of CLI‐mediated HCC development, Abcb4 [multidrug‐resistance 2 (Mdr2)]‐knockout (KO) mice, which express high levels of Gal1 in the liver. We generated double‐KO (dKO) Gal1‐KO/Mdr2‐KO mice on C57BL/6 and FVB/N genetic backgrounds and compared HCC development in the generated strains with their parental Mdr2‐KO strains. Loss of Gal1 increased liver injury, inflammation, fibrosis, and ductular reaction in dKO mice of both strains starting from an early age. Aged dKO mutants displayed earlier hepatocarcinogenesis and increased tumor size compared with control Mdr2‐KO mice. We found that osteopontin, a well‐known modulator of HCC development, and oncogenic proteins Ntrk2 (TrkB) and S100A4 were overexpressed in dKO compared with Mdr2‐KO livers. Our results demonstrate that in Mdr2‐KO mice, a model of CLI‐mediated HCC, Gal1‐mediated protection from hepatitis, liver fibrosis, and HCC initiation dominates over its known procarcinogenic activities at later stages of HCC development. These findings suggest that anti‐Gal1 treatments may not be applicable at all stages of CLI‐mediated HCC.—Potikha, T., Pappo, O., Mizrahi, L., Olam, D., Mailer, S. M., Rabinovich, G. A., Galun, E., Goldenberg, D. S. Lack of galectin‐1 exacerbates chronic hepatitis, liver fibrosis, and carcinogenesis in murine hepatocellular carcinoma model. FASEB J. 33, 7995–8007 (2019). http://www.fasebj.org

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confidence: 99%

Lack of galectin‐1 exacerbates chronic hepatitis, liver fibrosis, and carcinogenesis in murine hepatocellular carcinoma model

et al. 2019

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“…LGALS1 (galectin-1) has been broadly associated with the control of a wide range of innate and adaptive immune pathways including maintenance of foetal-maternal tolerance 29,30 , and AHR has been shown as an important transcription factor involved in IDO1 signalling in IDO1 signalling in DCs 31,32,33 , corroborating the importance of IDO1 for LC immunotolerance.…”

Section: Steadymentioning

confidence: 84%

Langerhans cells immunocompetency is critical for IDO1-dependent ability to induce tolerogenic T cells

Davies

Sirvent

Vallejo

et al. 2019

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Human epidermal Langerhans cells (LCs) can coordinate both immunogenic and tolerogenic immune responses, creating an attractive opportunity for immunomodulation strategies. To investigate transcriptional determinants of human primary LC tolerance we applied single cells RNA-sequencing combined with extensive functional analysis. Unsupervised clustering of single cell transcriptomes indicated that steady-state LC populations exist in a spectrum of immune activation between two states: immunocompetent and immature, distinguishable by high or low CD86 expression, respectively. Suprisingly, LC immunompetency was critical for the efficient induction of regulatory T cells during co-culture assays with naïve CD4+ T cells and expansion of autologous memory T cells. Consistently, LC tolerogenic potential was significantly enhanced upon migration from the epidermis. Transcriptional programmes underpinning LC immunocompetency, with increased expression of dendritic cell activation markers (CD83, HLA-DRA and CCR7), were complemented with expression of tolerogenic markers (IDO1, LGALS1 and AHR) in migrated LC. Using protein expression analysis and perturbation with inhibitors, we confirmed the role of IDO1 as a key regulator of LC tolerogenic responses induced during LC migration, identified AHR as a potential component of IDO1-regulatory feedback loop, and demonstrated LC-mediated tolerance can be modulated through treatment with dexamethasone, indicating an opportunity for targeted therapeutic interventions in inflammatory skin disease.

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“…Galectin-1 also displays higher avidity toward ligands bound to the cell surface than to those in solution. In this context, higher abundances of tetraantennary N-glycans and increased transcript levels of St3gal1 and St3gal6 in elicited macrophages may account for the concurrent increase in Lgals1 expression, which is known to promote an antiinflammatory phenotype (39).…”

Section: Discussionmentioning

confidence: 99%

Resident and elicited macrophages differ in expression of their glycomes and lectins

et al. 2020

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The pleiotropic functions of macrophages in immune defense, tissue repair, and maintenance of tissue homeostasis are supported by the heterogeneity in macrophage sub-populations that differ both in ontogeny and polarization. Although glycans and lectins are integral to macrophage function, little is known about the factors governing their expression. Here we show that the cellular glycome of murine peritoneal macrophages primarily reflects developmental origin and to a lesser degree, cellular polarization. Resident macrophages were characterized by a simple glycome, predominantly consisting of core 1 O-glycans, while elicited macrophages also expressed core 2 O-glycans, along with highly branched and extended complex-type N-glycans, that exhibited a higher N-acetylneuraminic acid:N-glycolylneuraminic acid ratio. Strikingly, our analysis revealed that resident and elicited macrophages express 139 lectin genes, with differential expression of 49 lectin genes, including galectins, Siglecs, and C-type lectins. These results suggest that regulation of self-glycan-protein complexes may be central to macrophage residence and recruitment.

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Galectin-1: A Jack-of-All-Trades in the Resolution of Acute and Chronic Inflammation

Cited by 152 publications

References 139 publications

Lack of galectin‐1 exacerbates chronic hepatitis, liver fibrosis, and carcinogenesis in murine hepatocellular carcinoma model

Lack of galectin‐1 exacerbates chronic hepatitis, liver fibrosis, and carcinogenesis in murine hepatocellular carcinoma model

Langerhans cells immunocompetency is critical for IDO1-dependent ability to induce tolerogenic T cells

Resident and elicited macrophages differ in expression of their glycomes and lectins

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