Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death

Toscano, Marta A.; Bianco, Germán A; Ilarregui, Juan M.; Croci, Diego O.; Correale, Jorge; Hernandez, Joseph D.; Zwirner, Norberto Walter; Poirier, Françoise; Riley, Eleanor M.; Baum, Linda G.; Rabinovich, Gabriel A.

doi:10.1038/ni1482

Cited by 580 publications

(742 citation statements)

References 52 publications

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“…These variables can dramatically change during thymic-development and peripheral activation and differentiation of T cells. [5,6,18,[38][39][40][41].…”

Section: Galectin-glycoprotein Lattices In T Cell Functionsmentioning

confidence: 99%

“…In contrast Th2 cells are protected from galectin-1 binding through differential α2,6-sialylation of cell surface glycoproteins (Figure 2). Galectin-1-deficient mice consistently developed greater antigen-specific Th1 and Th17 responses compared to wild-type mice [40]. In addition, other galectin members may contribute to this immunoregulatory effect, including galectin-9 which acts as a specific binding partner of Tim-3, a Th1-specific receptor, and selectively eliminates Th1 cells in vivo [46].…”

Section: Galectin-glycoprotein Lattices In T Cell Functionsmentioning

confidence: 99%

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Functions of cell surface galectin-glycoprotein lattices

Rabinovich

Toscano

Jackson

et al. 2007

Current Opinion in Structural Biology

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Programmed remodeling of cell surface glycans by the sequential action of specific glycosyltransferases, can control biological processes by generating or masking ligands for endogenous lectins. Galectins, a family of animal lectins with affinity for β-galactosides, can form multivalent complexes with cell surface glycoconjugates and deliver a variety of intracellular signals to modulate cell activation, differentiation, and survival. Recent efforts involving genetic or biochemical manipulation of O-and N-glycosylation pathways, as well as blockade of the synthesis of endogenous galectins, have illuminated essential roles for galectin-glycoprotein lattices in the control of biological processes including receptor turnover and endocytosis, host-pathogen interactions and immune cell activation and homeostasis.

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“…These variables can dramatically change during thymic-development and peripheral activation and differentiation of T cells. [5,6,18,[38][39][40][41].…”

Section: Galectin-glycoprotein Lattices In T Cell Functionsmentioning

confidence: 99%

Section: Galectin-glycoprotein Lattices In T Cell Functionsmentioning

confidence: 99%

Functions of cell surface galectin-glycoprotein lattices

Rabinovich

Toscano

Jackson

et al. 2007

Current Opinion in Structural Biology

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361

318

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“…Gal-1 and gal-9 have been described as negative regulators of the Th1 immune response [3] [26]. To assess this, we measured IFN-gamma and IL-10 production in co-cultures of CD4+ T cells with human moDCs preloaded with superantigen staphylococcal enterotoxin E (SEE) in the presence or absence of lactose (50mM), an inhibitor of galectin binding.…”

Section: Inhibition Of Galectin Binding Increases Ifn-gamma Productiomentioning

confidence: 99%

“…In vitro studies revealed that gal-1 limits the immune response, for example promoting apoptosis of Th-1 cells, inducing IL-10, or down-regulating pro-inflammatory cytokines [3,4].…”

Section: Introductionmentioning

confidence: 99%

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Psoriasis in humans is associated with down‐regulation of galectins in dendritic cells

Fuente

Pérez‐Gala

Bonay

et al. 2012

The Journal of Pathology

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2 ABSTRACT.We have investigated the expression and role of galectin-1 and other galectins in psoriasis and in the Th1/Th17 effector and dendritic cell responses associated with this chronic inflammatory skin condition. To determine differences between psoriasis patients and healthy donors, galectins expression was analyzed by RT-PCR assays in skin samples and specifically on epidermal and peripheral blood dendritic cells by immunofluorescence and flow cytometry.In skin of healthy donors galectins 1, 3 and 9 were expressed in a high proportion of Langerhans cells. Also, galectins were differentially expressed in peripheral blood dendritic cell subsets; galectin-1 and galectin-9 were highly expressed in peripheral myeloid dendritic cells compared with plasmacytoid dendritic cells. We found that non-lesional as well as lesional skin samples from psoriasis patients had low levels of galectin-1 at mRNA and protein level in parallel with low levels of IL-10 mRNA compared with skin from healthy patients. However, only lesional skin samples expressed high levels of

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BRAF inhibition curtails IFN‐gamma‐inducible PD‐L1 expression and upregulates the immunoregulatory protein galectin‐1 in melanoma cells

Górniak

Wasylecka-Juszczyńska

Ługowska

et al. 2020

Molecular Oncology

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Although melanoma is considered one of the most immunogenic malignancies, spontaneous T‐cell responses to melanoma antigens are ineffective due to tumor cell‐intrinsic or microenvironment‐driven immune evasion mechanisms. For example, oncogenic BRAF V600E mutation in melanoma cells fosters tumor immune escape by modulating cell immunogenicity and microenvironment composition. BRAF inhibition has been shown to increase melanoma cell immunogenicity, but these effects are transient and long‐term responses are uncommon. For these reasons, we aimed to further characterize the role of BRAF‐V600E mutation in the modulation of PD‐L1, a known immunoregulatory molecule, and galectin‐1 (Gal‐1), a potent immunoregulatory lectin involved in melanoma immune privilege. We report herein that vemurafenib downregulates IFN‐γ‐induced PD‐L1 expression by interfering with STAT1 activity and by decreasing PD‐L1 protein translation. Surprisingly, melanoma cells exposed to vemurafenib expressed higher levels of Gal‐1. In coculture experiments, A375 melanoma cells pretreated with vemurafenib induced apoptosis of interacting Jurkat T cells, whereas genetic inhibition of Gal‐1 in these cells restored the viability of cocultured T lymphocytes, indicating that Gal‐1 contributes to tumor immune escape. Importantly, Gal‐1 plasma concentration increased in patients progressing on BRAF/MEK inhibitor treatment, but remained stable in responding patients. Taken together, these results suggest a two‐faceted nature of BRAF inhibition‐associated immunomodulatory effects: an early immunostimulatory activity, mediated at least in part by decreased PD‐L1 expression, and a delayed immunosuppressive effect associated with Gal‐1 induction. Importantly, our observations suggest that Gal‐1 might be utilized as a potential biomarker and a putative therapeutic target in melanoma patients.

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Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death

Cited by 580 publications

References 52 publications

Functions of cell surface galectin-glycoprotein lattices

Functions of cell surface galectin-glycoprotein lattices

Psoriasis in humans is associated with down‐regulation of galectins in dendritic cells

BRAF inhibition curtails IFN‐gamma‐inducible PD‐L1 expression and upregulates the immunoregulatory protein galectin‐1 in melanoma cells

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