The Experts below are selected from a list of 21197514 Experts worldwide ranked by ideXlab platform
Elena Riboldi - One of the best experts on this subject based on the ideXlab platform.
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Abstract 2677: Role of CLEC4D in inflammation-driven liver carcinogenesis
Cancer Research, 2017Co-Authors: Elena Riboldi, Luca Di Tommaso, Nausicaa Clemente, Chiara Raggi, Simone Merlin, Elisa Forti, Antonia Follenzi, Fabio Pasqualini, Antonio SicaAbstract:Hepatocellular carcinoma (HCC) accounts for approximately 90% of all primary liver tumors and is the second most deadly cancer in the world. HCC commonly arises in a chronically damaged liver that contains large amounts of inflammation and fibrosis. Indeed, interactions among hepatocytes, stromal, and inflammatory cells create a complex microenvironment permissive to tumor development. Myeloid cells are crucial players in cancer-related inflammation. From transcriptional profiling of liver myeloid cells, we identified the gene encoding for the C-type lectin receptor CLEC4D as one of the genes upregulated during the inflammatory response that precedes cancer development in a spontaneous model of murine HCC. We hypothesized that CLEC4D may be involved in the molecular mechanisms that drive HCC pathogenesis. We used the murine model of diethylnitrosamine (DEN)-induced liver carcinogenesis and evaluated tumor growth in genetically modified mice lacking CLEC4D (CLEC4D KO mice), as compared to C57BL/6 wild type (WT) mice. We observed that tumor burden (number of tumors per mouse and tumor dimensions) was reduced in CLEC4D KO mice compared to WT mice. Gene expression analysis of tumor lesions showed that the tumor microenvironment of CLEC4D KO mice was less inflammatory. CLEC4D expression was then evaluated in surgical specimens and tissue microarrays from HCV+ HCC patients. CLEC4D-positive inflammatory cells (macrophages and granulocytes) were present both in the peritumor and in the tumor areas. The percentage of intratumor CLEC4D-positive cells inversely correlated with the degree of the lesion: CLEC4D expression was higher in dysplastic nodules compared to high grade HCCs. Our results indicate that the CLEC4D-dependent pathway contributes to the initiation and the progression of HCC. By targeting CLEC4D, we could modulate immune responses and provide an environment less favorable to tumor growth. An intervention at this level could represent a chemopreventive strategy to arrest the development of HCC in a cirrhotic liver.This work has been supported by Fondazione Cariplo, grant n° 2014-0962. Citation Format: Elena Riboldi, Luca Di Tommaso, Nausicaa Clemente, Chiara Raggi, Elisa Forti, Simone Merlin, Fabio Pasqualini, Antonia Follenzi, Antonio Sica. Role of CLEC4D in inflammation-driven liver carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2677. doi:10.1158/1538-7445.AM2017-2677
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Cell Depletion in Mice That Express Diphtheria Toxin Receptor under the Control of SiglecH Encompasses More Than Plasmacytoid Dendritic Cells
Journal of immunology (Baltimore Md. : 1950), 2014Co-Authors: Melissa Swiecki, Elena Riboldi, Yaming Wang, Susan Gilfillan, Alfred H.j. Kim, Amiran Dzutsev, William Vermi, Christiane Ruedl, Giorgio Trinchieri, Marco ColonnaAbstract:Plasmacytoid dendritic cells (pDC) produce IFN-I in response to viruses and are routinely identified in mice by SiglecH expression. SiglecH is a sialic acid-binding Ig-like lectin that has an immunomodulatory role during viral infections. In this study, we evaluated the impact of SiglecH deficiency on cytokine responses in the presence and absence of pDC. We found that lack of SiglecH enhanced IFN-I responses to viral infection, regardless of whether pDC were depleted. We also examined the expression pattern of SiglecH and observed that it was expressed by specialized macrophages and progenitors of classical dendritic cells and pDC. Accordingly, marginal zone macrophages and pDC precursors were eliminated in newly generated SiglecH-diphtheria toxin receptor (DTR)-transgenic (Tg) mice but not in CLEC4C-DTR-Tg mice after diphtheria toxin (DT) treatment. Using two bacterial models, we found that SiglecH-DTR-Tg mice injected with DT had altered bacterial uptake and were more susceptible to lethal Listeria monocytogenes infection than were DT-treated CLEC4C-DTR-Tg mice. Taken together, our findings suggest that lack of SiglecH may affect cytokine responses by cell types other than pDC during viral infections, perhaps by altering viral distribution or burden, and that cell depletion in SiglecH-DTR-Tg mice encompasses more than pDC.
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human c type lectin domain family 4 member c CLEC4C bdca 2 cd303 is a receptor for asialo galactosyl oligosaccharides
Journal of Biological Chemistry, 2011Co-Authors: Elena Riboldi, Marco Colonna, Roberta Daniele, Carmen Parola, Antonio Inforzato, Phoebe L. Arnold, Daniela Bosisio, Daved H. Fremont, Antonio Bastone, Silvano SozzaniAbstract:Plasmacytoid dendritic cells are specialized in the production of type I interferon (type I IFN), which promotes antiviral and antitumor responses, as well as autoimmune disorders. Activation of type I IFN secretion depends on the pattern recognition receptors TLR7 and TLR9, which sense microbial RNA and DNA, respectively. Type I IFN production is modulated by several receptors, including the type II C-type lectin domain family 4, member C (CLEC4C). The natural ligand of CLEC4C is unknown. To identify it, here we probed a glycan array with a soluble form of the CLEC4C ectodomain. We found that CLEC4C recognizes complex type sugars with terminal galactose. Importantly, soluble CLEC4C bound peripheral blood leukocytes and tumor cells that express glycans with galactose residues at the non-reducing ends. The positive and negative modulation of galactose residues on cell membranes was paralleled by the regulation of type I IFN secretion by plasmacytoid dendritic cells in co-culture experiments in vitro. These results suggest that the modulation in the expression of non-sialylated oligosaccharides by invading pathogens or transformed cells may affect type I IFN response and immune surveillance.
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Human C-type Lectin Domain Family 4, Member C (CLEC4C/BDCA-2/CD303) Is a Receptor for Asialo-galactosyl-oligosaccharides
The Journal of biological chemistry, 2011Co-Authors: Elena Riboldi, Marco Colonna, Roberta Daniele, Carmen Parola, Antonio Inforzato, Phoebe L. Arnold, Daniela Bosisio, Daved H. Fremont, Antonio Bastone, Silvano SozzaniAbstract:Plasmacytoid dendritic cells are specialized in the production of type I interferon (type I IFN), which promotes antiviral and antitumor responses, as well as autoimmune disorders. Activation of type I IFN secretion depends on the pattern recognition receptors TLR7 and TLR9, which sense microbial RNA and DNA, respectively. Type I IFN production is modulated by several receptors, including the type II C-type lectin domain family 4, member C (CLEC4C). The natural ligand of CLEC4C is unknown. To identify it, here we probed a glycan array with a soluble form of the CLEC4C ectodomain. We found that CLEC4C recognizes complex type sugars with terminal galactose. Importantly, soluble CLEC4C bound peripheral blood leukocytes and tumor cells that express glycans with galactose residues at the non-reducing ends. The positive and negative modulation of galactose residues on cell membranes was paralleled by the regulation of type I IFN secretion by plasmacytoid dendritic cells in co-culture experiments in vitro. These results suggest that the modulation in the expression of non-sialylated oligosaccharides by invading pathogens or transformed cells may affect type I IFN response and immune surveillance.
Silvano Sozzani - One of the best experts on this subject based on the ideXlab platform.
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human c type lectin domain family 4 member c CLEC4C bdca 2 cd303 is a receptor for asialo galactosyl oligosaccharides
Journal of Biological Chemistry, 2011Co-Authors: Elena Riboldi, Marco Colonna, Roberta Daniele, Carmen Parola, Antonio Inforzato, Phoebe L. Arnold, Daniela Bosisio, Daved H. Fremont, Antonio Bastone, Silvano SozzaniAbstract:Plasmacytoid dendritic cells are specialized in the production of type I interferon (type I IFN), which promotes antiviral and antitumor responses, as well as autoimmune disorders. Activation of type I IFN secretion depends on the pattern recognition receptors TLR7 and TLR9, which sense microbial RNA and DNA, respectively. Type I IFN production is modulated by several receptors, including the type II C-type lectin domain family 4, member C (CLEC4C). The natural ligand of CLEC4C is unknown. To identify it, here we probed a glycan array with a soluble form of the CLEC4C ectodomain. We found that CLEC4C recognizes complex type sugars with terminal galactose. Importantly, soluble CLEC4C bound peripheral blood leukocytes and tumor cells that express glycans with galactose residues at the non-reducing ends. The positive and negative modulation of galactose residues on cell membranes was paralleled by the regulation of type I IFN secretion by plasmacytoid dendritic cells in co-culture experiments in vitro. These results suggest that the modulation in the expression of non-sialylated oligosaccharides by invading pathogens or transformed cells may affect type I IFN response and immune surveillance.
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Human C-type Lectin Domain Family 4, Member C (CLEC4C/BDCA-2/CD303) Is a Receptor for Asialo-galactosyl-oligosaccharides
The Journal of biological chemistry, 2011Co-Authors: Elena Riboldi, Marco Colonna, Roberta Daniele, Carmen Parola, Antonio Inforzato, Phoebe L. Arnold, Daniela Bosisio, Daved H. Fremont, Antonio Bastone, Silvano SozzaniAbstract:Plasmacytoid dendritic cells are specialized in the production of type I interferon (type I IFN), which promotes antiviral and antitumor responses, as well as autoimmune disorders. Activation of type I IFN secretion depends on the pattern recognition receptors TLR7 and TLR9, which sense microbial RNA and DNA, respectively. Type I IFN production is modulated by several receptors, including the type II C-type lectin domain family 4, member C (CLEC4C). The natural ligand of CLEC4C is unknown. To identify it, here we probed a glycan array with a soluble form of the CLEC4C ectodomain. We found that CLEC4C recognizes complex type sugars with terminal galactose. Importantly, soluble CLEC4C bound peripheral blood leukocytes and tumor cells that express glycans with galactose residues at the non-reducing ends. The positive and negative modulation of galactose residues on cell membranes was paralleled by the regulation of type I IFN secretion by plasmacytoid dendritic cells in co-culture experiments in vitro. These results suggest that the modulation in the expression of non-sialylated oligosaccharides by invading pathogens or transformed cells may affect type I IFN response and immune surveillance.
Marco Colonna - One of the best experts on this subject based on the ideXlab platform.
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Cell Depletion in Mice That Express Diphtheria Toxin Receptor under the Control of SiglecH Encompasses More Than Plasmacytoid Dendritic Cells
Journal of immunology (Baltimore Md. : 1950), 2014Co-Authors: Melissa Swiecki, Elena Riboldi, Yaming Wang, Susan Gilfillan, Alfred H.j. Kim, Amiran Dzutsev, William Vermi, Christiane Ruedl, Giorgio Trinchieri, Marco ColonnaAbstract:Plasmacytoid dendritic cells (pDC) produce IFN-I in response to viruses and are routinely identified in mice by SiglecH expression. SiglecH is a sialic acid-binding Ig-like lectin that has an immunomodulatory role during viral infections. In this study, we evaluated the impact of SiglecH deficiency on cytokine responses in the presence and absence of pDC. We found that lack of SiglecH enhanced IFN-I responses to viral infection, regardless of whether pDC were depleted. We also examined the expression pattern of SiglecH and observed that it was expressed by specialized macrophages and progenitors of classical dendritic cells and pDC. Accordingly, marginal zone macrophages and pDC precursors were eliminated in newly generated SiglecH-diphtheria toxin receptor (DTR)-transgenic (Tg) mice but not in CLEC4C-DTR-Tg mice after diphtheria toxin (DT) treatment. Using two bacterial models, we found that SiglecH-DTR-Tg mice injected with DT had altered bacterial uptake and were more susceptible to lethal Listeria monocytogenes infection than were DT-treated CLEC4C-DTR-Tg mice. Taken together, our findings suggest that lack of SiglecH may affect cytokine responses by cell types other than pDC during viral infections, perhaps by altering viral distribution or burden, and that cell depletion in SiglecH-DTR-Tg mice encompasses more than pDC.
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Plasmacytoid Dendritic Cells Contribute to Systemic but Not Local Antiviral Responses to HSV Infections
PLoS pathogens, 2013Co-Authors: Melissa Swiecki, Yaming Wang, Susan Gilfillan, Marco ColonnaAbstract:Plasmacytoid dendritic cells (pDC) produce type I interferons (IFN-I) and proinflammatory cytokines in response to viruses; however, their contribution to antiviral immunity in vivo is unclear. In this study, we investigated the impact of pDC depletion on local and systemic antiviral responses to herpes simplex virus (HSV) infections using CLEC4C-DTR transgenic mice. We found that pDC do not appear to influence viral burden or survival after vaginal HSV-2 infection, nor do they seem to contribute to virus-specific CD8 T cell responses following subcutaneous HSV-1 infection. In contrast, pDC were important for early IFN-I production, proinflammatory cytokine production, NK cell activation and CD8 T cell responses during systemic HSV-2 and HSV-1 infections. Our data also indicate that unlike pDC, TLR3-expressing cells are important for promoting antiviral responses to HSV-1 regardless of the route of virus administration.
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Impact of pDC on vaginal HSV-2 infection.
2013Co-Authors: Melissa Swiecki, Yaming Wang, Susan Gilfillan, Marco ColonnaAbstract:CLEC4C-DTR Tg mice were injected subcutaneously with Depo-Provera or medroxyprogesterone acetate 7 days before vaginal HSV-2 infection. Mice were injected i.p. with PBS or DT 24 h before infection and every other day after. (A) Dotplots show pDC frequencies in lumbar lymph nodes of PBS or DT-treated mice at the time of infection. HSV-2 titers (B) and IFN-α levels (C) in vaginal/cervical tissues on day 2 p.i. after inoculation with 1×103 pfu. (D) Control or pDC-depleted mice were infected with 2×103 or 1×104 pfu of HSV-2 and survival was monitored for 15 days. Data are combined from or are representative of two independent experiments. Not significant (NS).
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human c type lectin domain family 4 member c CLEC4C bdca 2 cd303 is a receptor for asialo galactosyl oligosaccharides
Journal of Biological Chemistry, 2011Co-Authors: Elena Riboldi, Marco Colonna, Roberta Daniele, Carmen Parola, Antonio Inforzato, Phoebe L. Arnold, Daniela Bosisio, Daved H. Fremont, Antonio Bastone, Silvano SozzaniAbstract:Plasmacytoid dendritic cells are specialized in the production of type I interferon (type I IFN), which promotes antiviral and antitumor responses, as well as autoimmune disorders. Activation of type I IFN secretion depends on the pattern recognition receptors TLR7 and TLR9, which sense microbial RNA and DNA, respectively. Type I IFN production is modulated by several receptors, including the type II C-type lectin domain family 4, member C (CLEC4C). The natural ligand of CLEC4C is unknown. To identify it, here we probed a glycan array with a soluble form of the CLEC4C ectodomain. We found that CLEC4C recognizes complex type sugars with terminal galactose. Importantly, soluble CLEC4C bound peripheral blood leukocytes and tumor cells that express glycans with galactose residues at the non-reducing ends. The positive and negative modulation of galactose residues on cell membranes was paralleled by the regulation of type I IFN secretion by plasmacytoid dendritic cells in co-culture experiments in vitro. These results suggest that the modulation in the expression of non-sialylated oligosaccharides by invading pathogens or transformed cells may affect type I IFN response and immune surveillance.
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Human C-type Lectin Domain Family 4, Member C (CLEC4C/BDCA-2/CD303) Is a Receptor for Asialo-galactosyl-oligosaccharides
The Journal of biological chemistry, 2011Co-Authors: Elena Riboldi, Marco Colonna, Roberta Daniele, Carmen Parola, Antonio Inforzato, Phoebe L. Arnold, Daniela Bosisio, Daved H. Fremont, Antonio Bastone, Silvano SozzaniAbstract:Plasmacytoid dendritic cells are specialized in the production of type I interferon (type I IFN), which promotes antiviral and antitumor responses, as well as autoimmune disorders. Activation of type I IFN secretion depends on the pattern recognition receptors TLR7 and TLR9, which sense microbial RNA and DNA, respectively. Type I IFN production is modulated by several receptors, including the type II C-type lectin domain family 4, member C (CLEC4C). The natural ligand of CLEC4C is unknown. To identify it, here we probed a glycan array with a soluble form of the CLEC4C ectodomain. We found that CLEC4C recognizes complex type sugars with terminal galactose. Importantly, soluble CLEC4C bound peripheral blood leukocytes and tumor cells that express glycans with galactose residues at the non-reducing ends. The positive and negative modulation of galactose residues on cell membranes was paralleled by the regulation of type I IFN secretion by plasmacytoid dendritic cells in co-culture experiments in vitro. These results suggest that the modulation in the expression of non-sialylated oligosaccharides by invading pathogens or transformed cells may affect type I IFN response and immune surveillance.
Yurong Wen - One of the best experts on this subject based on the ideXlab platform.
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trimeric structure of the mouse kupffer cell c type lectin receptor clec4f
FEBS Letters, 2020Co-Authors: Zhenlin Ouyang, Fang Zheng, Jan Felix, Jinhong Zhou, Yingmei Pei, Irina Gutsche, Peter M Hwang, Joanne M Lemieux, Yurong WenAbstract:The C-type lectin receptor Clec4f has been identified as a specific surface marker for Kupffer cells, although its ortholog is absent in humans and its biological function remains elusive. Here, we report the crystal structure of a truncated mouse trimeric Clec4f. The orientation between the carbohydrate-recognition domain of Clec4f and its neck region differs from other C-type lectins, resulting in an observed distance of 45 A between the glycan-binding sites within the Clec4f trimer. Interestingly, the trimeric coiled-coil interface within its heptad neck region contains multiple polyglutamine interactions instead of the predominantly hydrophobic leucine zipper found in other C-type lectin receptors. The Clec4f trimeric structure displays unique features regarding its assembly and ligand recognition, shedding light on the evolution and diversity of the C-type lectin family.
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Trimeric structure of the mouse Kupffer cell C‐type lectin receptor Clec4f
FEBS Letters, 2019Co-Authors: Zhenlin Ouyang, Fang Zheng, Jan Felix, Jinhong Zhou, Yingmei Pei, Peter Hwang, M Joanne Lemieux, Irina Gutsche, Yurong WenAbstract:The C-type lectin receptor Clec4f has been identified as a specific surface marker for Kupffer cells, although its ortholog is absent in humans and its biological function remains elusive. Here, we report the crystal structure of a truncated mouse trimeric Clec4f. The orientation between the carbohydrate-recognition domain of Clec4f and its neck region differs from other C-type lectins, resulting in an observed distance of 45 Å between the glycan-binding sites within the Clec4f trimer. Interestingly, the trimeric coiled-coil interface within its heptad neck region contains multiple polyglutamine interactions instead of the predominantly hydrophobic leucine zipper found in other C-type lectin receptors. The Clec4f trimeric structure displays unique features regarding its assembly and ligand recognition, shedding light on the evolution and diversity of the C-type lectin family.
Daved H. Fremont - One of the best experts on this subject based on the ideXlab platform.
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human c type lectin domain family 4 member c CLEC4C bdca 2 cd303 is a receptor for asialo galactosyl oligosaccharides
Journal of Biological Chemistry, 2011Co-Authors: Elena Riboldi, Marco Colonna, Roberta Daniele, Carmen Parola, Antonio Inforzato, Phoebe L. Arnold, Daniela Bosisio, Daved H. Fremont, Antonio Bastone, Silvano SozzaniAbstract:Plasmacytoid dendritic cells are specialized in the production of type I interferon (type I IFN), which promotes antiviral and antitumor responses, as well as autoimmune disorders. Activation of type I IFN secretion depends on the pattern recognition receptors TLR7 and TLR9, which sense microbial RNA and DNA, respectively. Type I IFN production is modulated by several receptors, including the type II C-type lectin domain family 4, member C (CLEC4C). The natural ligand of CLEC4C is unknown. To identify it, here we probed a glycan array with a soluble form of the CLEC4C ectodomain. We found that CLEC4C recognizes complex type sugars with terminal galactose. Importantly, soluble CLEC4C bound peripheral blood leukocytes and tumor cells that express glycans with galactose residues at the non-reducing ends. The positive and negative modulation of galactose residues on cell membranes was paralleled by the regulation of type I IFN secretion by plasmacytoid dendritic cells in co-culture experiments in vitro. These results suggest that the modulation in the expression of non-sialylated oligosaccharides by invading pathogens or transformed cells may affect type I IFN response and immune surveillance.
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Human C-type Lectin Domain Family 4, Member C (CLEC4C/BDCA-2/CD303) Is a Receptor for Asialo-galactosyl-oligosaccharides
The Journal of biological chemistry, 2011Co-Authors: Elena Riboldi, Marco Colonna, Roberta Daniele, Carmen Parola, Antonio Inforzato, Phoebe L. Arnold, Daniela Bosisio, Daved H. Fremont, Antonio Bastone, Silvano SozzaniAbstract:Plasmacytoid dendritic cells are specialized in the production of type I interferon (type I IFN), which promotes antiviral and antitumor responses, as well as autoimmune disorders. Activation of type I IFN secretion depends on the pattern recognition receptors TLR7 and TLR9, which sense microbial RNA and DNA, respectively. Type I IFN production is modulated by several receptors, including the type II C-type lectin domain family 4, member C (CLEC4C). The natural ligand of CLEC4C is unknown. To identify it, here we probed a glycan array with a soluble form of the CLEC4C ectodomain. We found that CLEC4C recognizes complex type sugars with terminal galactose. Importantly, soluble CLEC4C bound peripheral blood leukocytes and tumor cells that express glycans with galactose residues at the non-reducing ends. The positive and negative modulation of galactose residues on cell membranes was paralleled by the regulation of type I IFN secretion by plasmacytoid dendritic cells in co-culture experiments in vitro. These results suggest that the modulation in the expression of non-sialylated oligosaccharides by invading pathogens or transformed cells may affect type I IFN response and immune surveillance.