Bahraoui, E.; Briant, L.; Chazal, N. E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein Article de journal Dans: Virol J, vol. 11, p. 214, 2014, ISSN: 1743-422X (Electronic)
1743-422X (Linking). @article{RN876,
title = {E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein},
author = {Bahraoui, E. and Briant, L. and Chazal, N.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25471526},
doi = {10.1186/s12985-014-0214-z},
issn = {1743-422X (Electronic)
1743-422X (Linking)},
year = {2014},
date = {2014-01-01},
journal = {Virol J},
volume = {11},
pages = {214},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Adoue, V; Schiavi, A; Light, N; Almlof, J C; Lundmark, P; Ge, B; Kwan, T; Caron, M; Ronnblom, L; Wang, C; Chen, S H; Goodall, A H; Cambien, F; Deloukas, P; Ouwehand, W H; Syvanen, A C; Pastinen, T Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs Article de journal Dans: Molecular Systems Biology, vol. 10, no. 10, p. 754, 2014. @article{Adoue2014,
title = {Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs},
author = {Adoue, V and Schiavi, A and Light, N and Almlof, J C and Lundmark, P and Ge, B and Kwan, T and Caron, M and Ronnblom, L and Wang, C and Chen, S H and Goodall, A H and Cambien, F and Deloukas, P and Ouwehand, W H and Syvanen, A C and Pastinen, T},
url = {http://msb.embopress.org/cgi/doi/10.15252/msb.20145114},
doi = {10.15252/msb.20145114},
year = {2014},
date = {2014-01-01},
journal = {Molecular Systems Biology},
volume = {10},
number = {10},
pages = {754},
publisher = {EMBO Press},
abstract = {Most complex disease‐associated genetic variants are located in non‐coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis‐ regulatory impact ( cis‐ rSNPs). We used AE mapping to identify cis‐ rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified monocyte samples and found 40–60% of these cis ‐rSNPs to be shared across cell types. We uncover a new class of cis ‐rSNPs, which disrupt footprint‐derived de novo motifs that are predominantly bound by repressive factors and are implicated in disease susceptibility through overlaps with GWAS SNPs. Finally, we provide the proof‐of‐principle for a new approach for genome‐wide functional validation of transcription factor–SNP interactions. By perturbing NF$kappa$B action in lymphoblasts, we identified 489 cis ‐regulated transcripts with altered AE after NF$kappa$B perturbation. Altogether, we perform a comprehensive analysis of cis ‐variation in four cell populations and provide new tools for the identification of functional variants associated to complex diseases.![][1]textless/imgtextgreaterA comprehensive analysis cis ‐variation in four cell‐populations uncovers a new‐class of cis ‐regulatory SNPs associated with repressor activity. Global analysis of the role of key regulators is achieved by combining allelic expression read‐outs with targeted perturbation of transcription factors.Mol Syst Biol. (2014) 10: 754 [1]: pending:yes},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Most complex disease‐associated genetic variants are located in non‐coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis‐ regulatory impact ( cis‐ rSNPs). We used AE mapping to identify cis‐ rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified monocyte samples and found 40–60% of these cis ‐rSNPs to be shared across cell types. We uncover a new class of cis ‐rSNPs, which disrupt footprint‐derived de novo motifs that are predominantly bound by repressive factors and are implicated in disease susceptibility through overlaps with GWAS SNPs. Finally, we provide the proof‐of‐principle for a new approach for genome‐wide functional validation of transcription factor–SNP interactions. By perturbing NF$kappa$B action in lymphoblasts, we identified 489 cis ‐regulated transcripts with altered AE after NF$kappa$B perturbation. Altogether, we perform a comprehensive analysis of cis ‐variation in four cell populations and provide new tools for the identification of functional variants associated to complex diseases.![][1]textless/imgtextgreaterA comprehensive analysis cis ‐variation in four cell‐populations uncovers a new‐class of cis ‐regulatory SNPs associated with repressor activity. Global analysis of the role of key regulators is achieved by combining allelic expression read‐outs with targeted perturbation of transcription factors.Mol Syst Biol. (2014) 10: 754 [1]: pending:yes |
Light, N; Adoue, V; Ge, B; Chen, S-H; Kwan, T; Pastinen, T Interrogation of allelic chromatin states in human cells by high-density ChIP-genotyping. Article de journal Dans: Epigenetics, vol. 9, no. 9, p. 1238–1251, 2014. @article{Light2014,
title = {Interrogation of allelic chromatin states in human cells by high-density ChIP-genotyping.},
author = {Light, N and Adoue, V and Ge, B and Chen, S-H and Kwan, T and Pastinen, T},
url = {http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25055051&retmode=ref&cmd=prlinks},
doi = {10.4161/epi.29920},
year = {2014},
date = {2014-01-01},
journal = {Epigenetics},
volume = {9},
number = {9},
pages = {1238--1251},
abstract = {Allele-specific (AS) assessment of chromatin has the potential to elucidate specific cis-regulatory mechanisms, which are predicted to underlie the majority of the known genetic associations to complex disease. However, development of chromatin landscapes at allelic resolution has been challenging since sites of variable signal strength require substantial read depths not commonly applied in sequencing based approaches. In this study, we addressed this by performing parallel analyses of input DNA and chromatin immunoprecipitates (ChIP) on high-density Illumina genotyping arrays. Allele-specificity for the histone modifications H3K4me1, H3K4me3, H3K27ac, H3K27me3, and H3K36me3 was assessed using ChIP samples generated from 14 lymphoblast and 6 fibroblast cell lines. AS-ChIP SNPs were combined into domains and validated using high-confidence ChIP-seq sites. We observed characteristic patterns of allelic-imbalance for each histone-modification around allele-specifically expressed transcripts. Notably, we found H3K4me1 to be significantly anti-correlated with allelic expression (AE) at transcription start sites, indicating H3K4me1 allelic imbalance as a marker of AE. We also found that allelic chromatin domains exhibit population and cell-type specificity as well as heritability within trios. Finally, we observed that a subset of allelic chromatin domains is regulated by DNase I-sensitive quantitative trait loci and that these domains are significantly enriched for genome-wide association studies hits, with autoimmune disease associated SNPs specifically enriched in lymphoblasts. This study provides the first genome-wide maps of allelic-imbalance for five histone marks. Our results provide new insights into the role of chromatin in cis-regulation and highlight the need for high-depth sequencing in ChIP-seq studies along with the need to improve allele-specificity of ChIP-enrichment.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Allele-specific (AS) assessment of chromatin has the potential to elucidate specific cis-regulatory mechanisms, which are predicted to underlie the majority of the known genetic associations to complex disease. However, development of chromatin landscapes at allelic resolution has been challenging since sites of variable signal strength require substantial read depths not commonly applied in sequencing based approaches. In this study, we addressed this by performing parallel analyses of input DNA and chromatin immunoprecipitates (ChIP) on high-density Illumina genotyping arrays. Allele-specificity for the histone modifications H3K4me1, H3K4me3, H3K27ac, H3K27me3, and H3K36me3 was assessed using ChIP samples generated from 14 lymphoblast and 6 fibroblast cell lines. AS-ChIP SNPs were combined into domains and validated using high-confidence ChIP-seq sites. We observed characteristic patterns of allelic-imbalance for each histone-modification around allele-specifically expressed transcripts. Notably, we found H3K4me1 to be significantly anti-correlated with allelic expression (AE) at transcription start sites, indicating H3K4me1 allelic imbalance as a marker of AE. We also found that allelic chromatin domains exhibit population and cell-type specificity as well as heritability within trios. Finally, we observed that a subset of allelic chromatin domains is regulated by DNase I-sensitive quantitative trait loci and that these domains are significantly enriched for genome-wide association studies hits, with autoimmune disease associated SNPs specifically enriched in lymphoblasts. This study provides the first genome-wide maps of allelic-imbalance for five histone marks. Our results provide new insights into the role of chromatin in cis-regulation and highlight the need for high-depth sequencing in ChIP-seq studies along with the need to improve allele-specificity of ChIP-enrichment. |
Kezic, Sanja; Novak, Natalija; Jakasa, Ivone; Jungersted, Jackob M; Simon, Michel; Brandner, Johanna M; Middelkamp-Hup, Maritza A; Weidinger, Stephan Skin barrier in atopic dermatitis. Article de journal Dans: Frontiers in bioscience (Landmark edition), vol. 19, p. 542–556, 2014, ISSN: 1093-4715 (Electronic). @article{Kezic2014,
title = {Skin barrier in atopic dermatitis.},
author = {Kezic, Sanja and Novak, Natalija and Jakasa, Ivone and Jungersted, Jackob M and Simon, Michel and Brandner, Johanna M and Middelkamp-Hup, Maritza A and Weidinger, Stephan},
doi = {10.2741/4225},
issn = {1093-4715 (Electronic)},
year = {2014},
date = {2014-01-01},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {19},
pages = {542--556},
abstract = {The skin represents the largest organ of the body and provides a vital interface between the body and the environment. Hereditary and acquired alterations of structural proteins and lipids of the stratum corneum and epidermal tight junctions leading to a diminished skin barrier function are major causative factors for a number of skin diseases, in particular atopic dermatitis (AD). This review summarizes current knowledge on the role of the skin barrier in AD with regard to pathogenesis and treatment, on the relationship between skin barrier abnormalities and immune aberrations, and on potential therapies aimed at repair of the skin barrier. Furthermore recent advances in the genetics of AD will be addressed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The skin represents the largest organ of the body and provides a vital interface between the body and the environment. Hereditary and acquired alterations of structural proteins and lipids of the stratum corneum and epidermal tight junctions leading to a diminished skin barrier function are major causative factors for a number of skin diseases, in particular atopic dermatitis (AD). This review summarizes current knowledge on the role of the skin barrier in AD with regard to pathogenesis and treatment, on the relationship between skin barrier abnormalities and immune aberrations, and on potential therapies aimed at repair of the skin barrier. Furthermore recent advances in the genetics of AD will be addressed. |
Mallet, A; Kypriotou, M; George, K; Leclerc, E; Rivero, D; Mazereeuw-Hautier, J; Serre, G; Huber, M; Jonca, N; Hohl, D Identification of the first nonsense CDSN mutation with expression of a truncated protein causing peeling skin syndrome type B. Article de journal Dans: The British journal of dermatology, vol. 169, no. 6, p. 1322–1325, 2013, ISSN: 1365-2133 (Electronic). @article{Mallet2013,
title = {Identification of the first nonsense CDSN mutation with expression of a truncated protein causing peeling skin syndrome type B.},
author = {Mallet, A and Kypriotou, M and George, K and Leclerc, E and Rivero, D and Mazereeuw-Hautier, J and Serre, G and Huber, M and Jonca, N and Hohl, D},
doi = {10.1111/bjd.12593},
issn = {1365-2133 (Electronic)},
year = {2013},
date = {2013-12-01},
journal = {The British journal of dermatology},
volume = {169},
number = {6},
pages = {1322--1325},
abstract = {BACKGROUND: Peeling skin disease (PSD), a generalized inflammatory form of peeling skin syndrome, is caused by autosomal recessive nonsense mutations in the corneodesmosin gene (CDSN). OBJECTIVES: To investigate a novel mutation in CDSN. METHODS: A 50-year-old white woman showed widespread peeling with erythema and elevated serum IgE. DNA sequencing, immunohistochemistry, Western blot and real-time polymerase chain reaction analyses of skin biopsies were performed in order to study the genetics and to characterize the molecular profile of the disease. RESULTS: Histology showed hyperkeratosis and acanthosis of the epidermis, and inflammatory infiltrates in the dermis. DNA sequencing revealed a homozygous mutation leading to a premature termination codon in CDSN: p.Gly142*. Protein analyses showed reduced expression of a 16-kDa corneodesmosin mutant in the upper epidermal layers, whereas the full-length protein was absent. CONCLUSIONS: These results are interesting regarding the genotype-phenotype correlations in diseases caused by CDSN mutations. The PSD-causing CDSN mutations identified heretofore result in total corneodesmosin loss, suggesting that PSD is due to full corneodesmosin deficiency. Here, we show for the first time that a mutant corneodesmosin can be stably expressed in some patients with PSD, and that this truncated protein is very probably nonfunctional.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Peeling skin disease (PSD), a generalized inflammatory form of peeling skin syndrome, is caused by autosomal recessive nonsense mutations in the corneodesmosin gene (CDSN). OBJECTIVES: To investigate a novel mutation in CDSN. METHODS: A 50-year-old white woman showed widespread peeling with erythema and elevated serum IgE. DNA sequencing, immunohistochemistry, Western blot and real-time polymerase chain reaction analyses of skin biopsies were performed in order to study the genetics and to characterize the molecular profile of the disease. RESULTS: Histology showed hyperkeratosis and acanthosis of the epidermis, and inflammatory infiltrates in the dermis. DNA sequencing revealed a homozygous mutation leading to a premature termination codon in CDSN: p.Gly142*. Protein analyses showed reduced expression of a 16-kDa corneodesmosin mutant in the upper epidermal layers, whereas the full-length protein was absent. CONCLUSIONS: These results are interesting regarding the genotype-phenotype correlations in diseases caused by CDSN mutations. The PSD-causing CDSN mutations identified heretofore result in total corneodesmosin loss, suggesting that PSD is due to full corneodesmosin deficiency. Here, we show for the first time that a mutant corneodesmosin can be stably expressed in some patients with PSD, and that this truncated protein is very probably nonfunctional. |
Delaby, Constance; Oustric, Vincent; Schmitt, Caroline; Muzeau, Francoise; Robreau, Anne-Marie; Letteron, Philippe; Couchi, Eric; Yu, Angel; Lyoumi, Saïd; Deybach, Jean-Charles; Puy, Herve; Karim, Zoubida; Beaumont, Carole; Grandchamp, Bernard; Demant, Peter; Gouya, Laurent Epistasis in iron metabolism: complex interactions between Cp, Mon1a, and Slc40a1 loci and tissue iron in mice Article de journal Dans: Mammalian Genome: Official Journal of the International Mammalian Genome Society, vol. 24, no. 11-12, p. 427–438, 2013, ISSN: 1432-1777. @article{delaby_epistasis_2013,
title = {Epistasis in iron metabolism: complex interactions between Cp, Mon1a, and Slc40a1 loci and tissue iron in mice},
author = {Delaby, Constance and Oustric, Vincent and Schmitt, Caroline and Muzeau, Francoise and Robreau, Anne-Marie and Letteron, Philippe and Couchi, Eric and Yu, Angel and Lyoumi, Saïd and Deybach, Jean-Charles and Puy, Herve and Karim, Zoubida and Beaumont, Carole and Grandchamp, Bernard and Demant, Peter and Gouya, Laurent},
doi = {10.1007/s00335-013-9479-6},
issn = {1432-1777},
year = {2013},
date = {2013-12-01},
journal = {Mammalian Genome: Official Journal of the International Mammalian Genome Society},
volume = {24},
number = {11-12},
pages = {427--438},
abstract = {Disorders of iron metabolism are among the most common acquired and constitutive diseases. Hemochromatosis has a solid genetic basis and in Northern European populations it is usually associated with homozygosity for the C282Y mutation in the HFE protein. However, the penetrance of this mutation is incomplete and the clinical presentation is highly variable. The rare and common variants identified so far as genetic modifiers of HFE-related hemochromatosis are unable to account for the phenotypic heterogeneity of this disorder. There are wide variations in the basal iron status of common inbred mouse strains, and this diversity may reflect the genetic background of the phenotypic diversity under pathological conditions. We therefore examined the genetic basis of iron homeostasis using quantitative trait loci mapping applied to the HcB-15 recombinant congenic strains for tissue and serum iron indices. Two highly significant QTL containing either the N374S Mon1a mutation or the Ferroportin locus were found to be major determinants in spleen and liver iron loading. Interestingly, when considering possible epistatic interactions, the effects of Mon1a on macrophage iron export are conditioned by the genotype at the Slc40a1 locus. Only mice that are C57BL/10ScSnA homozygous at both loci display a lower spleen iron burden. Furthermore, the liver-iron lowering effect of the N374S Mon1a mutation is observed only in mice that display a nonsense mutation in the Ceruloplasmin (Cp) gene. This study highlights the existence of genetic interactions between Cp, Mon1a, and the Slc40a1 locus in iron metabolism, suggesting that epistasis may be a crucial determinant of the variable biological and clinical presentations in iron disorders.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Disorders of iron metabolism are among the most common acquired and constitutive diseases. Hemochromatosis has a solid genetic basis and in Northern European populations it is usually associated with homozygosity for the C282Y mutation in the HFE protein. However, the penetrance of this mutation is incomplete and the clinical presentation is highly variable. The rare and common variants identified so far as genetic modifiers of HFE-related hemochromatosis are unable to account for the phenotypic heterogeneity of this disorder. There are wide variations in the basal iron status of common inbred mouse strains, and this diversity may reflect the genetic background of the phenotypic diversity under pathological conditions. We therefore examined the genetic basis of iron homeostasis using quantitative trait loci mapping applied to the HcB-15 recombinant congenic strains for tissue and serum iron indices. Two highly significant QTL containing either the N374S Mon1a mutation or the Ferroportin locus were found to be major determinants in spleen and liver iron loading. Interestingly, when considering possible epistatic interactions, the effects of Mon1a on macrophage iron export are conditioned by the genotype at the Slc40a1 locus. Only mice that are C57BL/10ScSnA homozygous at both loci display a lower spleen iron burden. Furthermore, the liver-iron lowering effect of the N374S Mon1a mutation is observed only in mice that display a nonsense mutation in the Ceruloplasmin (Cp) gene. This study highlights the existence of genetic interactions between Cp, Mon1a, and the Slc40a1 locus in iron metabolism, suggesting that epistasis may be a crucial determinant of the variable biological and clinical presentations in iron disorders. |
Charlier, Caroline M.; Wu, Yuan-Ju; Allart, Sophie; Malnou, Cécile E.; Schwemmle, Martin; Gonzalez-Dunia, Daniel Analysis of Borna Disease Virus Trafficking in Live Infected Cells by Using a Virus Encoding a Tetracysteine-Tagged P Protein Article de journal Dans: J Virol, vol. 87, no. 22, p. 12339–12348, 2013, ISSN: 1098-5514. @article{Charlier2013,
title = {Analysis of Borna Disease Virus Trafficking in Live Infected Cells by Using a Virus Encoding a Tetracysteine-Tagged P Protein},
author = {Caroline M. Charlier and Yuan-Ju Wu and Sophie Allart and Cécile E. Malnou and Martin Schwemmle and Daniel Gonzalez-Dunia},
doi = {10.1128/jvi.01127-13},
issn = {1098-5514},
year = {2013},
date = {2013-11-15},
urldate = {2013-11-15},
journal = {J Virol},
volume = {87},
number = {22},
pages = {12339--12348},
publisher = {American Society for Microbiology},
abstract = {<jats:title>ABSTRACT</jats:title>
<jats:p>Borna disease virus (BDV) is a nonsegmented, negative-stranded RNA virus characterized by noncytolytic persistent infection and replication in the nuclei of infected cells. To gain further insight on the intracellular trafficking of BDV components during infection, we sought to generate recombinant BDV (rBDV) encoding fluorescent fusion viral proteins. We successfully rescued a virus bearing a tetracysteine tag fused to BDV-P protein, which allowed assessment of the intracellular distribution and dynamics of BDV using real-time live imaging. In persistently infected cells, viral nuclear inclusions, representing viral factories tethered to chromatin, appeared to be extremely static and stable, contrasting with a very rapid and active trafficking of BDV components in the cytoplasm. Photobleaching (fluorescence recovery after photobleaching [FRAP] and fluorescence loss in photobleaching [FLIP]) imaging approaches revealed that BDV components were permanently and actively exchanged between cellular compartments, including within viral inclusions, albeit with a fraction of BDV-P protein not mobile in these structures, presumably due to its association with viral and/or cellular proteins. We also obtained evidence for transfer of viral material between persistently infected cells, with routing of the transferred components toward the cell nucleus. Finally, coculture experiments with noninfected cells allowed visualization of cell-to-cell BDV transmission and movement of the incoming viral material toward the nucleus. Our data demonstrate the potential of tetracysteine-tagged recombinant BDV for virus tracking during infection, which may provide novel information on the BDV life cycle and on the modalities of its interaction with the nuclear environment during viral persistence.</jats:p>},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
<jats:title>ABSTRACT</jats:title>
<jats:p>Borna disease virus (BDV) is a nonsegmented, negative-stranded RNA virus characterized by noncytolytic persistent infection and replication in the nuclei of infected cells. To gain further insight on the intracellular trafficking of BDV components during infection, we sought to generate recombinant BDV (rBDV) encoding fluorescent fusion viral proteins. We successfully rescued a virus bearing a tetracysteine tag fused to BDV-P protein, which allowed assessment of the intracellular distribution and dynamics of BDV using real-time live imaging. In persistently infected cells, viral nuclear inclusions, representing viral factories tethered to chromatin, appeared to be extremely static and stable, contrasting with a very rapid and active trafficking of BDV components in the cytoplasm. Photobleaching (fluorescence recovery after photobleaching [FRAP] and fluorescence loss in photobleaching [FLIP]) imaging approaches revealed that BDV components were permanently and actively exchanged between cellular compartments, including within viral inclusions, albeit with a fraction of BDV-P protein not mobile in these structures, presumably due to its association with viral and/or cellular proteins. We also obtained evidence for transfer of viral material between persistently infected cells, with routing of the transferred components toward the cell nucleus. Finally, coculture experiments with noninfected cells allowed visualization of cell-to-cell BDV transmission and movement of the incoming viral material toward the nucleus. Our data demonstrate the potential of tetracysteine-tagged recombinant BDV for virus tracking during infection, which may provide novel information on the BDV life cycle and on the modalities of its interaction with the nuclear environment during viral persistence.</jats:p> |
Lyoumi, Said; Lefebvre, Thibaud; Karim, Zoubida; Gouya, Laurent; Puy, Hervé PXR-ALAS1: a key regulatory pathway in liver toxicity induced by isoniazid-rifampicin antituberculosis treatment Article de journal Dans: Clinics and Research in Hepatology and Gastroenterology, vol. 37, no. 5, p. 439–441, 2013, ISSN: 2210-741X. @article{lyoumi_pxr-alas1_2013,
title = {PXR-ALAS1: a key regulatory pathway in liver toxicity induced by isoniazid-rifampicin antituberculosis treatment},
author = {Lyoumi, Said and Lefebvre, Thibaud and Karim, Zoubida and Gouya, Laurent and Puy, Hervé},
doi = {10.1016/j.clinre.2013.06.010},
issn = {2210-741X},
year = {2013},
date = {2013-11-01},
journal = {Clinics and Research in Hepatology and Gastroenterology},
volume = {37},
number = {5},
pages = {439--441},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Moulouel, Boualem; Houamel, Dounia; Delaby, Constance; Tchernitchko, Dimitri; Vaulont, Sophie; Letteron, Philippe; Thibaudeau, Olivier; Puy, Hervé; Gouya, Laurent; Beaumont, Carole; Karim, Zoubida Hepcidin regulates intrarenal iron handling at the distal nephron Article de journal Dans: Kidney International, vol. 84, no. 4, p. 756–766, 2013, ISSN: 1523-1755. @article{moulouel_hepcidin_2013,
title = {Hepcidin regulates intrarenal iron handling at the distal nephron},
author = {Moulouel, Boualem and Houamel, Dounia and Delaby, Constance and Tchernitchko, Dimitri and Vaulont, Sophie and Letteron, Philippe and Thibaudeau, Olivier and Puy, Hervé and Gouya, Laurent and Beaumont, Carole and Karim, Zoubida},
doi = {10.1038/ki.2013.142},
issn = {1523-1755},
year = {2013},
date = {2013-10-01},
journal = {Kidney International},
volume = {84},
number = {4},
pages = {756--766},
abstract = {Hepcidin, the key regulatory hormone of iron homeostasis, and iron carriers such as transferrin receptor1 (TFR1), divalent metal transporter1 (DMT1), and ferroportin (FPN) are expressed in kidney. Whether hepcidin plays an intrinsic role in the regulation of renal iron transport is unknown. Here, we analyzed the renal handling of iron in hemochromatosis Hepc(-/-) and Hjv(-/-) mouse models, as well as in phenylhydrazine (PHZ)-treated mice. We found a marked medullary iron deposition in the kidneys of Hepc(-/-) mice, and iron leak in the urine. The kidneys of Hepc(-/-) mice exhibited a concomitant decrease in TFR1 and increase in ferritin and FPN expression. Increased FPN abundance was restricted to the thick ascending limb (TAL). DMT1 protein remained unaffected despite a significant decrease of its mRNA level, suggesting that DMT1 protein is stabilized in the absence of hepcidin. Treatment of kidney sections from Hepc(-/-) mice with hepcidin decreased DMT1 protein, an effect confirmed in renal cell lines where hepcidin markedly decreased (55)Fe transport. In the kidneys of Hjv(-/-) mice exhibiting low hepcidin expression, the iron overload was similar to that in the kidneys of Hepc(-/-) mice. However, in PHZ mice, iron accumulation resulting from hemoglobin leak was detected in the proximal tubule. Thus, kidneys exhibit a tissue-specific handling of iron that depends on the extra iron source. Hepcidin may control the expression of iron transporters to prevent renal iron overload.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hepcidin, the key regulatory hormone of iron homeostasis, and iron carriers such as transferrin receptor1 (TFR1), divalent metal transporter1 (DMT1), and ferroportin (FPN) are expressed in kidney. Whether hepcidin plays an intrinsic role in the regulation of renal iron transport is unknown. Here, we analyzed the renal handling of iron in hemochromatosis Hepc(-/-) and Hjv(-/-) mouse models, as well as in phenylhydrazine (PHZ)-treated mice. We found a marked medullary iron deposition in the kidneys of Hepc(-/-) mice, and iron leak in the urine. The kidneys of Hepc(-/-) mice exhibited a concomitant decrease in TFR1 and increase in ferritin and FPN expression. Increased FPN abundance was restricted to the thick ascending limb (TAL). DMT1 protein remained unaffected despite a significant decrease of its mRNA level, suggesting that DMT1 protein is stabilized in the absence of hepcidin. Treatment of kidney sections from Hepc(-/-) mice with hepcidin decreased DMT1 protein, an effect confirmed in renal cell lines where hepcidin markedly decreased (55)Fe transport. In the kidneys of Hjv(-/-) mice exhibiting low hepcidin expression, the iron overload was similar to that in the kidneys of Hepc(-/-) mice. However, in PHZ mice, iron accumulation resulting from hemoglobin leak was detected in the proximal tubule. Thus, kidneys exhibit a tissue-specific handling of iron that depends on the extra iron source. Hepcidin may control the expression of iron transporters to prevent renal iron overload. |
Liblau, Roland S.; Gonzalez-Dunia, Daniel; Wiendl, Heinz; Zipp, Frauke Neurons as targets for T cells in the nervous system Article de journal Dans: Trends in Neurosciences, vol. 36, no. 6, p. 315–324, 2013, ISSN: 0166-2236. @article{Liblau2013,
title = {Neurons as targets for T cells in the nervous system},
author = {Roland S. Liblau and Daniel Gonzalez-Dunia and Heinz Wiendl and Frauke Zipp},
doi = {10.1016/j.tins.2013.01.008},
issn = {0166-2236},
year = {2013},
date = {2013-06-00},
urldate = {2013-06-00},
journal = {Trends in Neurosciences},
volume = {36},
number = {6},
pages = {315--324},
publisher = {Elsevier BV},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Suberbielle, Elsa; Sanchez, Pascal E; Kravitz, Alexxai V; Wang, Xin; Ho, Kaitlyn; Eilertson, Kirsten; Devidze, Nino; Kreitzer, Anatol C; Mucke, Lennart Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β Article de journal Dans: Nat Neurosci, vol. 16, no. 5, p. 613–621, 2013, ISSN: 1546-1726. @article{Suberbielle2013,
title = {Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β},
author = {Elsa Suberbielle and Pascal E Sanchez and Alexxai V Kravitz and Xin Wang and Kaitlyn Ho and Kirsten Eilertson and Nino Devidze and Anatol C Kreitzer and Lennart Mucke},
doi = {10.1038/nn.3356},
issn = {1546-1726},
year = {2013},
date = {2013-05-00},
urldate = {2013-05-00},
journal = {Nat Neurosci},
volume = {16},
number = {5},
pages = {613--621},
publisher = {Springer Science and Business Media LLC},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Pellerin, Laurence; Henry, Julie; Hsu, Chiung-Yueh; Balica, Stéfana; Jean-Decoster, Catherine; Méchin, Marie-Claire; Hansmann, Britta; Rodriguez, Elke; Weindinger, Stefan; Schmitt, Anne-Marie; Serre, Guy; Paul, Carle; Simon, Michel Defects of filaggrin-like proteins in both lesional and nonlesional atopic skin. Article de journal Dans: The Journal of allergy and clinical immunology, vol. 131, no. 4, p. 1094–1102, 2013, ISSN: 1097-6825 (Electronic). @article{Pellerin2013,
title = {Defects of filaggrin-like proteins in both lesional and nonlesional atopic skin.},
author = {Pellerin, Laurence and Henry, Julie and Hsu, Chiung-Yueh and Balica, Stéfana and Jean-Decoster, Catherine and Méchin, Marie-Claire and Hansmann, Britta and Rodriguez, Elke and Weindinger, Stefan and Schmitt, Anne-Marie and Serre, Guy and Paul, Carle and Simon, Michel},
doi = {10.1016/j.jaci.2012.12.1566},
issn = {1097-6825 (Electronic)},
year = {2013},
date = {2013-04-01},
journal = {The Journal of allergy and clinical immunology},
volume = {131},
number = {4},
pages = {1094--1102},
abstract = {BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a disturbed epidermal barrier. In a subset of patients, this is explained by nonsense mutations in the gene encoding filaggrin (FLG). OBJECTIVES: We sought to evaluate the respective role of FLG mutations and proinflammatory cytokines and to assess the expression of FLG, hornerin (HRNR), and FLG2, 2 FLG-like proteins, which are involved in epidermal barrier functions, in normal skin and both lesional and nonlesional skin of patients with AD. METHODS: An FLG-genotyped cohort of 73 adults with AD and 73 aged-matched control subjects was analyzed by using immunohistochemistry and immunoblotting. Normal primary human keratinocytes were differentiated in either the absence or presence of IL-4, IL-13, and IL-25. RESULTS: Compared with control subjects, FLG, HRNR, and FLG2 were detected at significantly lower levels in the skin of patients with AD, irrespective of their FLG genotype. The reduction was greater in lesional compared with nonlesional skin. In addition, the proFLG/FLG ratio was found to be higher in the skin of wild-type patients than in control subjects. Cytokine treatment of keratinocytes induced a dramatic reduction in FLG, FLG2, and HRNR expression both at the mRNA and protein levels. CONCLUSION: The stratum corneum of lesional but also clinically unaffected skin of adults with AD is abnormal, with reduced expression of FLG and FLG-like proteins. In addition to nonsense mutations, proinflammatory cytokines and some defects in the proFLG processing can contribute to the FLG downregulation. Our study suggests that skin inflammation reduces the expression of FLG-like proteins, contributing to the AD-related epidermal barrier dysfunction.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a disturbed epidermal barrier. In a subset of patients, this is explained by nonsense mutations in the gene encoding filaggrin (FLG). OBJECTIVES: We sought to evaluate the respective role of FLG mutations and proinflammatory cytokines and to assess the expression of FLG, hornerin (HRNR), and FLG2, 2 FLG-like proteins, which are involved in epidermal barrier functions, in normal skin and both lesional and nonlesional skin of patients with AD. METHODS: An FLG-genotyped cohort of 73 adults with AD and 73 aged-matched control subjects was analyzed by using immunohistochemistry and immunoblotting. Normal primary human keratinocytes were differentiated in either the absence or presence of IL-4, IL-13, and IL-25. RESULTS: Compared with control subjects, FLG, HRNR, and FLG2 were detected at significantly lower levels in the skin of patients with AD, irrespective of their FLG genotype. The reduction was greater in lesional compared with nonlesional skin. In addition, the proFLG/FLG ratio was found to be higher in the skin of wild-type patients than in control subjects. Cytokine treatment of keratinocytes induced a dramatic reduction in FLG, FLG2, and HRNR expression both at the mRNA and protein levels. CONCLUSION: The stratum corneum of lesional but also clinically unaffected skin of adults with AD is abnormal, with reduced expression of FLG and FLG-like proteins. In addition to nonsense mutations, proinflammatory cytokines and some defects in the proFLG processing can contribute to the FLG downregulation. Our study suggests that skin inflammation reduces the expression of FLG-like proteins, contributing to the AD-related epidermal barrier dysfunction. |
Salles, J. P.; Laurencin-Dalicieux, S.; Conte-Auriol, F.; Briand-Mesange, F.; Gennero, I. Bone defects in LPA receptor genetically modified mice Article de journal Dans: Biochim Biophys Acta, vol. 1831, no. 1, p. 93-8, 2013, ISSN: 0006-3002 (Print)
0006-3002 (Linking). @article{RN37,
title = {Bone defects in LPA receptor genetically modified mice},
author = {Salles, J. P. and Laurencin-Dalicieux, S. and Conte-Auriol, F. and Briand-Mesange, F. and Gennero, I.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/22867754},
doi = {10.1016/j.bbalip.2012.07.018},
issn = {0006-3002 (Print)
0006-3002 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {Biochim Biophys Acta},
volume = {1831},
number = {1},
pages = {93-8},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Davignon, J. L.; Hayder, M.; Baron, M.; Boyer, J. F.; Constantin, A.; Apparailly, F.; Poupot, R.; Cantagrel, A. Targeting monocytes/macrophages in the treatment of rheumatoid arthritis Article de journal Dans: Rheumatology (Oxford), vol. 52, no. 4, p. 590-8, 2013, ISSN: 1462-0332 (Electronic)
1462-0324 (Linking). @article{RN15b,
title = {Targeting monocytes/macrophages in the treatment of rheumatoid arthritis},
author = {Davignon, J. L. and Hayder, M. and Baron, M. and Boyer, J. F. and Constantin, A. and Apparailly, F. and Poupot, R. and Cantagrel, A.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/23204551},
doi = {10.1093/rheumatology/kes304},
issn = {1462-0332 (Electronic)
1462-0324 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {Rheumatology (Oxford)},
volume = {52},
number = {4},
pages = {590-8},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Fruchon, S.; Caminade, A. M.; Abadie, C.; Davignon, J. L.; Combette, J. M.; Turrin, C. O.; Poupot, R. An azabisphosphonate-capped poly(phosphorhydrazone) dendrimer for the treatment of endotoxin-induced uveitis Article de journal Dans: Molecules, vol. 18, no. 8, p. 9305-16, 2013, ISSN: 1420-3049 (Electronic)
1420-3049 (Linking). @article{RN20,
title = {An azabisphosphonate-capped poly(phosphorhydrazone) dendrimer for the treatment of endotoxin-induced uveitis},
author = {Fruchon, S. and Caminade, A. M. and Abadie, C. and Davignon, J. L. and Combette, J. M. and Turrin, C. O. and Poupot, R.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/23921793},
doi = {10.3390/molecules18089305},
issn = {1420-3049 (Electronic)
1420-3049 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {Molecules},
volume = {18},
number = {8},
pages = {9305-16},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Guerder, S.; Joncker, N.; Mahiddine, K.; Serre, L. Dendritic cells in tolerance and autoimmune diabetes Article de journal Dans: Curr Opin Immunol, vol. 25, no. 6, p. 670-5, 2013, ISSN: 1879-0372 (Electronic)
0952-7915 (Linking). @article{RN7b,
title = {Dendritic cells in tolerance and autoimmune diabetes},
author = {Guerder, S. and Joncker, N. and Mahiddine, K. and Serre, L.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/24168964},
doi = {10.1016/j.coi.2013.10.004},
issn = {1879-0372 (Electronic)
0952-7915 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {Curr Opin Immunol},
volume = {25},
number = {6},
pages = {670-5},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Pasquet, L.; Douet, J. Y.; Sparwasser, T.; Romagnoli, P.; van Meerwijk, J. P. M. Long-term prevention of chronic allograft rejection by regulatory T-cell immunotherapy involves host Foxp3-expressing T cells Article de journal Dans: Blood, vol. 121, no. 21, p. 4303-10, 2013, ISSN: 1528-0020 (Electronic)
0006-4971 (Linking). @article{RN173,
title = {Long-term prevention of chronic allograft rejection by regulatory T-cell immunotherapy involves host Foxp3-expressing T cells},
author = {Pasquet, L. and Douet, J. Y. and Sparwasser, T. and Romagnoli, P. and van Meerwijk, J. P. M.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23580663},
doi = {10.1182/blood-2012-08-452037},
issn = {1528-0020 (Electronic)
0006-4971 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {Blood},
volume = {121},
number = {21},
pages = {4303-10},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Tellier, J.; Andrianjaka, A.; Vicente, R.; Thiault, N.; Enault, G.; Garchon, H. J.; van Meerwijk, J. P. M.; Romagnoli, P. Increased thymic development of regulatory T cells in NOD mice is functionally dissociated from type I diabetes susceptibility Article de journal Dans: Eur J Immunol, vol. 43, no. 5, p. 1356-62, 2013, ISSN: 1521-4141 (Electronic)
0014-2980 (Linking). @article{RN174,
title = {Increased thymic development of regulatory T cells in NOD mice is functionally dissociated from type I diabetes susceptibility},
author = {Tellier, J. and Andrianjaka, A. and Vicente, R. and Thiault, N. and Enault, G. and Garchon, H. J. and van Meerwijk, J. P. M. and Romagnoli, P.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23400928},
doi = {10.1002/eji.201243142},
issn = {1521-4141 (Electronic)
0014-2980 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {Eur J Immunol},
volume = {43},
number = {5},
pages = {1356-62},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Pelletier, L.; Savignac, M. Ca(2+) signaling in T-cell subsets with a focus on the role of cav1 channels: possible implications in therapeutics Article de journal Dans: Front Immunol, vol. 4, p. 150, 2013, ISSN: 1664-3224 (Print)
1664-3224 (Linking). @article{RN15,
title = {Ca(2+) signaling in T-cell subsets with a focus on the role of cav1 channels: possible implications in therapeutics},
author = {Pelletier, L. and Savignac, M.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/23801988},
doi = {10.3389/fimmu.2013.00150},
issn = {1664-3224 (Print)
1664-3224 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {Front Immunol},
volume = {4},
pages = {150},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Robert, V.; Triffaux, E.; Savignac, M.; Pelletier, L. Singularities of calcium signaling in effector T-lymphocytes Article de journal Dans: Biochim Biophys Acta, vol. 1833, no. 7, p. 1595-602, 2013, ISSN: 0006-3002 (Print)
0006-3002 (Linking). @article{RN16b,
title = {Singularities of calcium signaling in effector T-lymphocytes},
author = {Robert, V. and Triffaux, E. and Savignac, M. and Pelletier, L.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/23266355},
doi = {10.1016/j.bbamcr.2012.12.001},
issn = {0006-3002 (Print)
0006-3002 (Linking)},
year = {2013},
date = {2013-01-01},
journal = {Biochim Biophys Acta},
volume = {1833},
number = {7},
pages = {1595-602},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
