Tumor-associated glycoprotein (TAG-72) is a natural ligand for the C-type lectin-like domain that induces anti-inflammatory orientation of early pregnancy decidual CD1a+ dendritic cells

Laškarin, Gordana; Redžović, Arnela; Vlastelić, Ivan; Haller, Herman; Medančić, Suzana Sršen; Solinas, Graziella; Rukavina, Daniel

doi:10.1016/j.jri.2010.10.001

Cited by 15 publications

(24 citation statements)

References 37 publications

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“…Muc 1 acts as a physical barrier between the cell surface and external environment, thus protecting cells from microorganisms, toxins, or proteolytic factors, as well as preventing trophoblast invasion with equal efficiency [30, 31]. We recently demonstrated the absence of tumour-associated TAG-72 in uterine decidua of normal and pathological human pregnancies (nonembryonic pregnancy and missed abortion) at the implantation sites although TAG-72 was present in epithelial cells at and away from the tubal implantation site of an ectopic pregnancy [32]. Moreover, our recent in vitro studies confirmed the interaction between Muc 1 [33] and TAG-72 [32] with APCs at the maternal-foetal interface [32].…”

Section: Accessory Regulators Of Alloreactivitymentioning

confidence: 99%

“…We recently demonstrated the absence of tumour-associated TAG-72 in uterine decidua of normal and pathological human pregnancies (nonembryonic pregnancy and missed abortion) at the implantation sites although TAG-72 was present in epithelial cells at and away from the tubal implantation site of an ectopic pregnancy [32]. Moreover, our recent in vitro studies confirmed the interaction between Muc 1 [33] and TAG-72 [32] with APCs at the maternal-foetal interface [32]. Our experiments suggested that they participate in the maturation of CD1a + DCs and macrophages and critically influence their phenotype, cytokine and chemokine production, and functions, as shown in Figure 1(a).…”

Section: Accessory Regulators Of Alloreactivitymentioning

confidence: 99%

“…MR contains 8 and CD209 contains 7 extracellular carbohydrate recognition domains [63], indicating that these cells can bind to highly glycosylated molecules such as TAG-72 [64] (Figure 1(a)). Indeed, TAG-72 competes with mannan, which is a primordial ligand for the carbohydrate recognition domain [64], and it binds MR and CD209 on decidual CD1a + cells in vitro [32]. This binding is important because ligands binding the carbohydrate recognition domain of MR can activate an anti-inflammatory and a tolerogenic response in monocyte-derived DCs [25] such as decidual DCs [32].…”

Section: Mucins Suppress Alloreactivity At the Maternal-foetal Intmentioning

confidence: 99%

“…Indeed, TAG-72 competes with mannan, which is a primordial ligand for the carbohydrate recognition domain [64], and it binds MR and CD209 on decidual CD1a + cells in vitro [32]. This binding is important because ligands binding the carbohydrate recognition domain of MR can activate an anti-inflammatory and a tolerogenic response in monocyte-derived DCs [25] such as decidual DCs [32]. Indeed, after TAG-72 stimulation, decidual CD1a + cells show significantly decreased CD83 molecules, likely due to its active secretion [65].…”

Section: Mucins Suppress Alloreactivity At the Maternal-foetal Intmentioning

confidence: 99%

“…TAG-72-treated decidual CD1a + cells were unable to stimulate the proliferation of syngeneic decidual T cells [32], mostly of the CD45 + phenotype [70] (Figure 1(a)), although they significantly stimulated the proliferation of allogeneic, naïve cord blood T cells [32]. Furthermore, allogeneic T-cells cocultured with monocyte-derived DCs, which were matured using an antimannose receptor monoclonal antibody of the PAM-1 clone in vitro , initially proliferated but later became anergic and behaved as suppressor/regulatory cells [25].…”

Section: Effects Of Mucins On Decidual T-cell Functionsmentioning

confidence: 99%

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Mucins Help to Avoid Alloreactivity at the Maternal Fetal Interface

Redžović

Laškarin

Dominović

et al. 2013

Clinical and Developmental Immunology

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During gestation, many different mechanisms act to render the maternal immune system tolerant to semi-allogeneic trophoblast cells of foetal origin, including those mediated via mucins that are expressed during the peri-implantation period in the uterus. Tumour- associated glycoprotein-72 (TAG-72) enhances the already established tolerogenic features of decidual dendritic cells with the inability to progress towards Th1 immune orientation due to lowered interferon (IFN)-γ and interleukin (IL)-15 expression. Mucine 1 (Muc 1) supports alternative activation of decidual macrophages, restricts the proliferation of decidual regulatory CD56+ bright natural killer (NK) cells, and downregulates their cytotoxic potential, including cytotoxic mediator protein expression. Removing TAG-72 and Muc 1 from the eutopic implantation site likely contributes to better control of trophoblast invasion by T cells and NK cells and appears to have important immunologic advantages for successful implantation, in addition to mechanical advantages. However, these processes may lead to uncontrolled trophoblast growth after implantation, inefficient defence against infection or tumours, and elimination of unwanted immunocompetent cells at the maternal-foetal interface. The use of mucins by tumour cells to affect the local microenvironment in order to avoid the host immune response and to promote local tumour growth, invasion, and metastasis confirms this postulation.

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Section: Accessory Regulators Of Alloreactivitymentioning

confidence: 99%

Section: Accessory Regulators Of Alloreactivitymentioning

confidence: 99%

Section: Mucins Suppress Alloreactivity At the Maternal-foetal Intmentioning

confidence: 99%

Section: Mucins Suppress Alloreactivity At the Maternal-foetal Intmentioning

confidence: 99%

Section: Effects Of Mucins On Decidual T-cell Functionsmentioning

confidence: 99%

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Mucins Help to Avoid Alloreactivity at the Maternal Fetal Interface

Redžović

Laškarin

Dominović

et al. 2013

Clinical and Developmental Immunology

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The Ligands of C-Type Lectins

Foster

Bird

Timmer

et al. 2016

C-Type Lectin Receptors in Immunity

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Galectin-1 binds mucin in human trophoblast

Bojić‐Trbojević

Krivokuća

Kolundžić

et al. 2014

Histochem Cell Biol

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Mucins are multifunctional highly glycosylated proteins expressed by the female reproductive tract. Differential expression of MUC1 and MUC15 has been shown in trophoblast. This study was undertaken to establish the distribution of mucin(s) in cytotrophoblast cell cultures using anti-bovine submaxillary mucin (BSM) and to investigate the possibility of MUC1/mucin(s) being a binding partner of trophoblast galectin-1. MUC1 is demonstrated here using immunocytochemistry on isolated cytotrophoblast and the HTR-8/SVneo extravillous trophoblast cell line but detection of additional trophoblast mucins cannot be excluded. Western blot analysis showed similar bands ranging from 30 to >200 kDa with anti-BSM and the well-known mucin antibodies HMFG1 and B72.3. Immunocytochemistry and cell-based ELISA data were found to support that all of the antibodies used are reactive with BSM, suggesting the presence of shared epitopes between BSM and trophoblast mucin(s). Binding of galectin-1 to trophoblast MUC1/mucin(s) was analyzed using a solid-phase assay and co-immunoprecipitation. Recombinant galectin-1 binding to isolated trophoblast mucin in solid-phase assay was sensitive to lactose, a carbohydrate inhibitor of galectin binding. In whole HTR-8/SVneo lysates, ~200 kDa mucin was detected in galectin-1 immunoprecipitates, while endogenous galectin-1 was present in BSM-immunoprecipitates. Furthermore, double fluorescence immunocytochemistry showed overlap of galectin-1 and trophoblast mucins at the plasma membrane of HTR-8/SVneo cells. These results suggest that trophoblast mucin(s) could act as binding partners of galectin-1, in a carbohydrate-dependent manner.

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Tumor-associated glycoprotein (TAG-72) is a natural ligand for the C-type lectin-like domain that induces anti-inflammatory orientation of early pregnancy decidual CD1a+ dendritic cells

Cited by 15 publications

References 37 publications

Mucins Help to Avoid Alloreactivity at the Maternal Fetal Interface

Mucins Help to Avoid Alloreactivity at the Maternal Fetal Interface

The Ligands of C-Type Lectins

Galectin-1 binds mucin in human trophoblast

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