@article{d,

title = {Guanine nucleotide exchange factor RABGEF1 regulates keratinocyte-intrinsic signaling to maintain skin homeostasis},

author = {Marichal, T. and Gaudenzio, N. and El Abbas, S. and Sibilano, R. and Zurek, O. and Starkl, P. and Reber, L. L. and Pirottin, D. and Kim, J. and Chambon, P. and Roers, A. and Antoine, N. and Kawakami, Y. and Kawakami, T. and Bureau, F. and Tam, S. Y. and Tsai, M. and Galli, S. J.},

year  = {2016},

date = {2016-01-01},

journal = {J Clin Invest},

volume = {126},

number = {12},

pages = {4497-4515},

abstract = {Epidermal keratinocytes form a structural and immune barrier that is essential for skin homeostasis. However, the mechanisms that regulate epidermal barrier function are incompletely understood. Here we have found that keratinocyte-specific deletion of the gene encoding RAB guanine nucleotide exchange factor 1 (RABGEF1, also known as RABEX-5) severely impairs epidermal barrier function in mice and induces an allergic cutaneous and systemic phenotype. RABGEF1-deficient keratinocytes exhibited aberrant activation of the intrinsic IL-1R/MYD88/NF-κB signaling pathway and MYD88-dependent abnormalities in expression of structural proteins that contribute to skin barrier function. Moreover, ablation of MYD88 signaling in RABGEF1-deficient keratinocytes or deletion of Il1r1 restored skin homeostasis and prevented development of skin inflammation. We further demonstrated that epidermal RABGEF1 expression is reduced in skin lesions of humans diagnosed with either atopic dermatitis or allergic contact dermatitis as well as in an inducible mouse model of allergic dermatitis. Our findings reveal a key role for RABGEF1 in dampening keratinocyte-intrinsic MYD88 signaling and sustaining epidermal barrier function in mice, and suggest that dysregulation of RABGEF1 expression may contribute to epidermal barrier dysfunction in allergic skin disorders in mice and humans. Thus, RABGEF1-mediated regulation of IL-1R/MYD88 signaling might represent a potential therapeutic target.},

note = {Marichal, Thomas 

Gaudenzio, Nicolas 

El Abbas, Sophie 

Sibilano, Riccardo 

Zurek, Oliwia 

Starkl, Philipp 

Reber, Laurent L 

Pirottin, Dimitri 

Kim, Jinah 

Chambon, Pierre 

Roers, Axel 

Antoine, Nadine 

Kawakami, Yuko 

Kawakami, Toshiaki 

Bureau, Fabrice 

Tam, See-Ying 

Tsai, Mindy 

Galli, Stephen J 

T32 AI007290/AI/NIAID NIH HHS/United States 

R01 HL124283/HL/NHLBI NIH HHS/United States 

R01 AI023990/AI/NIAID NIH HHS/United States 

R01 AR067145/AR/NIAMS NIH HHS/United States 

K99 AI110645/AI/NIAID NIH HHS/United States 

R01 CA072074/CA/NCI NIH HHS/United States 

R37 AI023990/AI/NIAID NIH HHS/United States 

R01 AI070813/AI/NIAID NIH HHS/United States 

R01 AR064418/AR/NIAMS NIH HHS/United States 

Research Support, N.I.H., Extramural 

Research Support, Non-U.S. Gov't 

J Clin Invest. 2016 Dec 1;126(12):4497-4515. doi: 10.1172/JCI86359. Epub 2016 Nov 7.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Neutrophils are not required for resolution of acute gouty arthritis in mice},

author = {Reber, L. L. and Gaudenzio, N. and Starkl, P. and Galli, S. J.},

year  = {2016},

date = {2016-01-01},

journal = {Nat Med},

volume = {22},

number = {12},

pages = {1382-1384},

note = {Reber, Laurent L 

Gaudenzio, Nicolas 

Starkl, Philipp 

Galli, Stephen J 

K99 AI110645/AI/NIAID NIH HHS/United States 

R01 AR067145/AR/NIAMS NIH HHS/United States 

U19 AI104209/AI/NIAID NIH HHS/United States 

R21 NS080062/NS/NINDS NIH HHS/United States 

Comment 

Letter 

Research Support, N.I.H., Extramural 

Research Support, Non-U.S. Gov't 

United States 

Nat Med. 2016 Dec 6;22(12):1382-1384. doi: 10.1038/nm.4216.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {A TNFRSF14-FcɛRI-mast cell pathway contributes to development of multiple features of asthma pathology in mice},

author = {Sibilano, R. and Gaudenzio, N. and DeGorter, M. K. and Reber, L. L. and Hernandez, J. D. and Starkl, P. M. and Zurek, O. W. and Tsai, M. and Zahner, S. and Montgomery, S. B. and Roers, A. and Kronenberg, M. and Yu, M. and Galli, S. J.},

year  = {2016},

date = {2016-01-01},

journal = {Nat Commun},

volume = {7},

pages = {13696},

abstract = {Asthma has multiple features, including airway hyperreactivity, inflammation and remodelling. The TNF superfamily member TNFSF14 (LIGHT), via interactions with the receptor TNFRSF14 (HVEM), can support T(H)2 cell generation and longevity and promote airway remodelling in mouse models of asthma, but the mechanisms by which TNFSF14 functions in this setting are incompletely understood. Here we find that mouse and human mast cells (MCs) express TNFRSF14 and that TNFSF14:TNFRSF14 interactions can enhance IgE-mediated MC signalling and mediator production. In mouse models of asthma, TNFRSF14 blockade with a neutralizing antibody administered after antigen sensitization, or genetic deletion of Tnfrsf14, diminishes plasma levels of antigen-specific IgG(1) and IgE antibodies, airway hyperreactivity, airway inflammation and airway remodelling. Finally, by analysing two types of genetically MC-deficient mice after engrafting MCs that either do or do not express TNFRSF14, we show that TNFRSF14 expression on MCs significantly contributes to the development of multiple features of asthma pathology.},

note = {Sibilano, Riccardo 

Gaudenzio, Nicolas 

DeGorter, Marianne K 

Reber, Laurent L 

Hernandez, Joseph D 

Starkl, Philipp M 

Zurek, Oliwia W 

Tsai, Mindy 

Zahner, Sonja 

Montgomery, Stephen B 

Roers, Axel 

Kronenberg, Mitchell 

Yu, Mang 

Galli, Stephen J 

T32 AI007290/AI/NIAID NIH HHS/United States 

Research Support, N.I.H., Extramural 

Research Support, Non-U.S. Gov't 

Nat Commun. 2016 Dec 16;7:13696. doi: 10.1038/ncomms13696.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {IgE antibodies, FcεRIα, and IgE-mediated local anaphylaxis can limit snake venom toxicity},

author = {Starkl, P. and Marichal, T. and Gaudenzio, N. and Reber, L. L. and Sibilano, R. and Tsai, M. and Galli, S. J.},

year  = {2016},

date = {2016-01-01},

journal = {J Allergy Clin Immunol},

volume = {137},

number = {1},

pages = {246-257 e11},

abstract = {BACKGROUND: Type 2 cytokine-related immune responses associated with development of antigen-specific IgE antibodies can contribute to pathology in patients with allergic diseases and to fatal anaphylaxis. However, recent findings in mice indicate that IgE also can enhance defense against honeybee venom. OBJECTIVE: We tested whether IgE antibodies, IgE-dependent effector mechanisms, and a local anaphylactic reaction to an unrelated antigen can enhance defense against Russell viper venom (RVV) and determined whether such responses can be influenced by immunization protocol or mouse strain. METHODS: We compared the resistance of RVV-immunized wild-type, IgE-deficient, and Fcer1a-deficient mice after injection of a potentially lethal dose of RVV. RESULTS: A single prior exposure to RVV enhanced the ability of wild-type mice, but not mice lacking IgE or functional FcεRI, to survive challenge with a potentially lethal amount of RVV. Moreover, IgE-dependent local passive cutaneous anaphylaxis in response to challenge with an antigen not naturally present in RVV significantly enhanced resistance to the venom. Finally, we observed different effects on resistance to RVV or honeybee venom in BALB/c versus C57BL/6 mice that had received a second exposure to that venom before challenge with a high dose of that venom. CONCLUSION: These observations illustrate the potential benefit of IgE-dependent effector mechanisms in acquired host defense against venoms. The extent to which type 2 immune responses against venoms can decrease pathology associated with envenomation seems to be influenced by the type of venom, the frequency of venom exposure, and the genetic background of the host.},

note = {Starkl, Philipp 

Marichal, Thomas 

Gaudenzio, Nicolas 

Reber, Laurent Lionel 

Sibilano, Riccardo 

Tsai, Mindy 

Galli, Stephen Joseph 

R01 AI023990/AI/NIAID NIH HHS/United States 

CA072074/CA/NCI NIH HHS/United States 

K99 AI110645/AI/NIAID NIH HHS/United States 

AI070813/AI/NIAID NIH HHS/United States 

AI023990/AI/NIAID NIH HHS/United States 

R01 CA072074/CA/NCI NIH HHS/United States 

K99AI110645/AI/NIAID NIH HHS/United States 

UL1 RR025744/RR/NCRR NIH HHS/United States 

UL1 TR001085/TR/NCATS NIH HHS/United States 

R37 AI023990/AI/NIAID NIH HHS/United States 

R01 AI070813/AI/NIAID NIH HHS/United States 

Research Support, N.I.H., Extramural 

Research Support, Non-U.S. Gov't 

J Allergy Clin Immunol. 2016 Jan;137(1):246-257.e11. doi: 10.1016/j.jaci.2015.08.005. Epub 2015 Sep 26.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN15b,

title = {The RNA-binding protein TTP is a global post-transcriptional regulator of feedback control in inflammation},

author = {Tiedje, C. and Diaz-Munoz, M. D. and Trulley, P. and Ahlfors, H. and Laass, K. and Blackshear, P. J. and Turner, M. and Gaestel, M.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/27220464},

doi = {10.1093/nar/gkw474},

issn = {1362-4962 (Electronic) 

0305-1048 (Linking)},

year  = {2016},

date = {2016-01-01},

journal = {Nucleic Acids Res},

volume = {44},

number = {15},

pages = {7418-40},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN16b,

title = {RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence},

author = {Galloway, A. and Saveliev, A. and Lukasiak, S. and Hodson, D. J. and Bolland, D. and Balmanno, K. and Ahlfors, H. and Monzon-Casanova, E. and Mannurita, S. C. and Bell, L. S. and Andrews, S. and Diaz-Munoz, M. D. and Cook, S. J. and Corcoran, A. and Turner, M.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/27102483},

doi = {10.1126/science.aad5978},

issn = {1095-9203 (Electronic) 

0036-8075 (Linking)},

year  = {2016},

date = {2016-01-01},

journal = {Science},

volume = {352},

number = {6284},

pages = {453-9},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chavanas2016,

title = {Peroxisome proliferator-activated receptor γ (PPARγ) activation: A key determinant of neuropathogeny during congenital infection by cytomegalovirus},

author = {Stéphane Chavanas},

doi = {10.1080/23262133.2016.1231654},

issn = {2326-2133},

year  = {2016},

date = {2016-01-00},

urldate = {2016-01-00},

journal = {Neurogenesis},

volume = {3},

number = {1},

publisher = {Informa UK Limited},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Suberbielle2015,

title = {DNA repair factor BRCA1 depletion occurs in Alzheimer brains and impairs cognitive function in mice},

author = {Elsa Suberbielle and Biljana Djukic and Mark Evans and Daniel H. Kim and Praveen Taneja and Xin Wang and Mariel Finucane and Joseph Knox and Kaitlyn Ho and Nino Devidze and Eliezer Masliah and Lennart Mucke},

doi = {10.1038/ncomms9897},

issn = {2041-1723},

year  = {2015},

date = {2015-12-22},

urldate = {2015-12-22},

journal = {Nat Commun},

volume = {6},

number = {1},

publisher = {Springer Science and Business Media LLC},

abstract = {<jats:title>Abstract</jats:title><jats:p>Maintaining DNA integrity is vital for all cells and organisms. Defective DNA repair may contribute to neurological disorders, including Alzheimer’s disease (AD). We found reduced levels of BRCA1, but not of other DNA repair factors, in the brains of AD patients and human amyloid precursor protein (hAPP) transgenic mice. Amyloid-β oligomers reduced BRCA1 levels in primary neuronal cultures. In wild-type mice, knocking down neuronal BRCA1 in the dentate gyrus caused increased DNA double-strand breaks, neuronal shrinkage, synaptic plasticity impairments, and learning and memory deficits, but not apoptosis. Low levels of hAPP/Amyloid-β overexpression exacerbated these effects. Physiological neuronal activation increased BRCA1 levels, whereas stimulating predominantly extrasynaptic <jats:italic>N</jats:italic>-methyl-<jats:sc>D</jats:sc>-aspartate receptors promoted the proteasomal degradation of BRCA1. We conclude that BRCA1 is regulated by neuronal activity, protects the neuronal genome, and critically supports neuronal integrity and cognitive functions. Pathological accumulation of Aβ depletes neuronal BRCA1, which may contribute to cognitive deficits in AD.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Valentin2015,

title = {Increased expression of caspase-1 and interleukin-18 in peeling skin disease, and a novel mutation of corneodesmosin.},

author = {Valentin, Frederic and Oji, Vinzenz and Hausser, Ingrid and Liebau, Eva and Tarinski, Tatjana and Metze, Dieter and Breitkreutz, Dirk and Traupe, Heiko and Jonca, Nathalie and Terheyden, Patrick},

doi = {10.2340/00015555-2142},

issn = {1651-2057 (Electronic)},

year  = {2015},

date = {2015-11-01},

journal = {Acta dermato-venereologica},

volume = {95},

number = {8},

pages = {1019--1021},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{LeLamer2015,

title = {Defects of corneocyte structural proteins and epidermal barrier in atopic dermatitis.},

author = {Le Lamer, Marina and Pellerin, Laurence and Reynier, Marie and Cau, Laura and Pendaries, Valérie and Leprince, Corinne and Méchin, Marie-Claire and Serre, Guy and Paul, Carle and Simon, Michel},

doi = {10.1515/hsz-2015-0141},

issn = {1437-4315 (Electronic)},

year  = {2015},

date = {2015-11-01},

journal = {Biological chemistry},

volume = {396},

number = {11},

pages = {1163--1179},

abstract = {The main function of the epidermis is to establish a vital multifunctional barrier between the body and its external environment. A defective epidermal barrier is one of the key features of atopic dermatitis (AD), a chronic and relapsing inflammatory skin disorder that affects up to 20% of children and 2-3% of adults and often precedes the development of allergic rhinitis and asthma. This review summarizes recent discoveries on the origin of the skin barrier alterations in AD at the structural protein level, including hereditary and acquired components. The consequences of the epidermal barrier alteration on our current understanding of the pathogenesis of AD, and its possible implications on the treatment of patients, are discussed here.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Viret2015,

title = {The T Cell Repertoire-Diversifying Enzyme TSSP Contributes to Thymic Selection of Diabetogenic CD4 T Cell Specificities Reactive to ChgA and IAPP Autoantigens},

author = {Viret, C. and Mahiddine, K. and Baker, R.L. and Haskins, K. and Guerder, S },

url = {https://www.ncbi.nlm.nih.gov/pubmed/26209627},

doi = {10.4049/jimmunol.1401683},

year  = {2015},

date = {2015-09-01},

journal = {J Immunol },

volume = {5},

number = {195},

pages = {1964-1973},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lefebvre_lc-msms_2015,

title = {LC-MS/MS method for hepcidin-25 measurement in human and mouse serum: clinical and research implications in iron disorders},

author = {Lefebvre, Thibaud and Dessendier, Nathalie and Houamel, Dounia and Ialy-Radio, Nathalie and Kannengiesser, Caroline and Manceau, Hana and Beaumont, Carole and Nicolas, Gael and Gouya, Laurent and Puy, Hervé and Karim, Zoubida},

doi = {10.1515/cclm-2014-1093},

issn = {1437-4331},

year  = {2015},

date = {2015-09-01},

journal = {Clinical Chemistry and Laboratory Medicine},

volume = {53},

number = {10},

pages = {1557--1567},

abstract = {BACKGROUND: The peptide hepcidin plays a central role in regulating dietary iron absorption and body iron distribution. This 25-amino acid hormone is produced and secreted predominantly by hepatocytes. Hepcidin has been suggested as a promising diagnostic marker for iron-related disorders. However, its accurate quantification for clinical use remains so far challenging. In this report we describe a highly specific and quantitative serum hepcidin method using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). 

MATERIAL: The analytical validation included the determination of the limit of detection, of quantification, repeatability, reproducibility and linearity. This assay was developed for human and mouse hepcidin. The human assay was performed on serum patients with unexplained microcytic anemia. We applied our LC-MS/MS method for quantifying hepcidin-1 in mouse in various conditions: inflammation, hemolytic anemia, Hamp-1, Hjv and Hfe KO mice. RESULTS: We show that the LC-MS/MS is suitable for accurate determination of hepcidin-25 in clinical samples, thereby representing a useful tool for the clinical diagnosis and follow-up of iron-related diseases. In mouse, a strong correlation between hepatic Hamp-1 mRNA expression and serum hepcidin-1 levels was found (r=0.88; p=0.0002) and the expected variations in mouse models of iron disorders were observed. 

CONCLUSIONS: Therefore, we propose this adaptive LC-MS/MS method as a suitable method for accurate determination of hepcidin-25 in clinical samples and as a major tool contributing to the clinical diagnosis, follow-up and management of iron-related disorders. It also opens new avenues to measure hepcidin in animal models without interspecies antigenic limitations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{karim_porphyrias_2015,

title = {Porphyrias: A 2015 update},

author = {Karim, Zoubida and Lyoumi, Said and Nicolas, Gael and Deybach, Jean-Charles and Gouya, Laurent and Puy, Hervé},

doi = {10.1016/j.clinre.2015.05.009},

issn = {2210-741X},

year  = {2015},

date = {2015-09-01},

journal = {Clinics and Research in Hepatology and Gastroenterology},

volume = {39},

number = {4},

pages = {412--425},

abstract = {The hereditary porphyrias comprise a group of eight metabolic disorders of the heme biosynthesis pathway. Each porphyria is caused by abnormal function at a separate enzymatic step resulting in a specific accumulation of heme precursors. Porphyrias are classified as hepatic or erythropoietic, based on the organ system in which heme precursors (δ-aminolevulinic acid [ALA], porphobilinogen and porphyrins) are overproduced. Clinically, porphyrias are characterized by acute neurovisceral symptoms, skin lesions or both. However, most if not all the porphyrias impair hepatic or gastrointestinal function. Acute hepatic porphyrias present with severe abdominal pain, nausea, constipation, confusion and seizure, which may be life threatening, and patients are at risk of hepatocellular carcinoma without cirrhosis. Porphyria Cutanea presents with skin fragility and blisters, and patients are at risk of hepatocellular carcinoma with liver iron overload. Erythropoietic protoporphyria and X-linked protoporphyria present with acute painful photosensitivity, and patients are at risk of acute liver failure. Altogether, porphyrias are still underdiagnosed, but once they are suspected, early diagnosis based on measurement of biochemical metabolites that accumulate in the blood, urine, or feces is essential so specific treatment can be started as soon as possible and long-term liver complications are prevented. Screening families to identify presymptomatic carriers is also crucial to prevent overt disease and chronic hepatic complications.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{homedan_mitochondrial_2015,

title = {Mitochondrial energetic defects in muscle and brain of a Hmbs-/- mouse model of acute intermittent porphyria},

author = {Homedan, Chadi and Schmitt, Caroline and Laafi, Jihane and Gueguen, Naïg and Desquiret-Dumas, Valérie and Lenglet, Hugo and Karim, Zoubida and Gouya, Laurent and Deybach, Jean-Charles and Simard, Gilles and Puy, Hervé and Malthièry, Yves and Reynier, Pascal},

doi = {10.1093/hmg/ddv222},

issn = {1460-2083},

year  = {2015},

date = {2015-09-01},

journal = {Human Molecular Genetics},

volume = {24},

number = {17},

pages = {5015--5023},

abstract = {Acute intermittent porphyria (AIP), an autosomal dominant metabolic disease (MIM #176000), is due to a deficiency of hydroxymethylbilane synthase (HMBS), which catalyzes the third step of the heme biosynthetic pathway. The clinical expression of the disease is mainly neurological, involving the autonomous, central and peripheral nervous systems. We explored mitochondrial oxidative phosphorylation (OXPHOS) in the brain and skeletal muscle of the Hmbs(-/-) mouse model first in the basal state (BS), and then after induction of the disease with phenobarbital and treatment with heme arginate (HA). The modification of the respiratory parameters, determined in mice in the BS, reflected a spontaneous metabolic energetic adaptation to HMBS deficiency. Phenobarbital induced a sharp alteration of the oxidative metabolism with a significant decrease of ATP production in skeletal muscle that was restored by treatment with HA. This OXPHOS defect was due to deficiencies in complexes I and II in the skeletal muscle whereas all four respiratory chain complexes were affected in the brain. To date, the pathogenesis of AIP has been mainly attributed to the neurotoxicity of aminolevulinic acid and heme deficiency. Our results show that mitochondrial energetic failure also plays an important role in the expression of the disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pallet_high_2015,

title = {High prevalence of and potential mechanisms for chronic kidney disease in patients with acute intermittent porphyria},

author = {Pallet, Nicolas and Mami, Iadh and Schmitt, Caroline and Karim, Zoubida and François, Arnaud and Rabant, Marion and Nochy, Dominique and Gouya, Laurent and Deybach, Jean-Charles and Xu-Dubois, Yichum and Thervet, Eric and Puy, Hervé and Karras, Alexandre},

doi = {10.1038/ki.2015.97},

issn = {1523-1755},

year  = {2015},

date = {2015-08-01},

journal = {Kidney International},

volume = {88},

number = {2},

pages = {386--395},

abstract = {Acute intermittent porphyria (AIP) is a genetic disorder of the synthesis of heme caused by a deficiency in hydroxymethylbilane synthase (HMBS), leading to the overproduction of the porphyrin precursors δ-aminolevulinic acid and porphobilinogen. The aim of this study is to describe the clinical and biological characteristics, the renal pathology, and the cellular mechanisms of chronic kidney disease associated with AIP. A total of 415 patients with HMBS deficiency followed up in the French Porphyria Center were enrolled in 2003 in a population-based study. A follow-up study was conducted in 2013, assessing patients for clinical, biological, and histological parameters. In vitro models were used to determine whether porphyrin precursors promote tubular and endothelial cytotoxicity. Chronic kidney disease occurred in up to 59% of the symptomatic AIP patients, with a decline in the glomerular filtration rate of textasciitilde1 ml/min per 1.73 m(2) annually. Proteinuria was absent in the vast majority of the cases. The renal pathology was a chronic tubulointerstitial nephropathy, associated with a fibrous intimal hyperplasia and focal cortical atrophy. Our experimental data provide evidence that porphyrin precursors promote endoplasmic reticulum stress, apoptosis, and epithelial phenotypic changes in proximal tubular cells. In conclusion, the diagnosis of chronic kidney disease associated with AIP should be considered in cases of chronic tubulointerstitial nephropathy and/or focal cortical atrophy with severe proliferative arteriosclerosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Leghmar2015,

title = {Cytomegalovirus Infection Triggers the Secretion of the PPARγ Agonists 15-Hydroxyeicosatetraenoic Acid (15-HETE) and 13-Hydroxyoctadecadienoic Acid (13-HODE) in Human Cytotrophoblasts and Placental Cultures},

author = {Kaoutar Leghmar and Nicolas Cenac and Maude Rolland and Hélène Martin and Benjamin Rauwel and Justine Bertrand-Michel and Pauline Le Faouder and Mélinda Bénard and Charlotte Casper and Christian Davrinche and Thierry Fournier and Stéphane Chavanas},

editor = {Juliet Spencer},

doi = {10.1371/journal.pone.0132627},

issn = {1932-6203},

year  = {2015},

date = {2015-07-14},

urldate = {2015-07-14},

journal = {PLoS ONE},

volume = {10},

number = {7},

publisher = {Public Library of Science (PLoS)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Li2015,

title = {Human Cytomegalovirus Infection Dysregulates the Localization and Stability of NICD1 and Jag1 in Neural Progenitor Cells},

author = {Xiao-Jun Li and Xi-Juan Liu and Bo Yang and Ya-Ru Fu and Fei Zhao and Zhang-Zhou Shen and Ling-Feng Miao and Simon Rayner and Stéphane Chavanas and Hua Zhu and William J. Britt and Qiyi Tang and Michael A. McVoy and Min-Hua Luo},

editor = {R. M. Sandri-Goldin},

doi = {10.1128/jvi.00351-15},

issn = {1098-5514},

year  = {2015},

date = {2015-07-00},

urldate = {2015-07-00},

journal = {J Virol},

volume = {89},

number = {13},

pages = {6792--6804},

publisher = {American Society for Microbiology},

abstract = {<jats:title>ABSTRACT</jats:title><jats:p>Human cytomegalovirus (HCMV) infection of the developing fetus frequently results in major neural developmental damage. In previous studies, HCMV was shown to downregulate neural progenitor/stem cell (NPC) markers and induce abnormal differentiation. As Notch signaling plays a vital role in the maintenance of stem cell status and is a switch that governs NPC differentiation, the effect of HCMV infection on the Notch signaling pathway in NPCs was investigated. HCMV downregulated mRNA levels of Notch1 and its ligand, Jag1, and reduced protein levels and altered the intracellular localization of Jag1 and the intracellular effector form of Notch1, NICD1. These effects required HCMV gene expression and appeared to be mediated through enhanced proteasomal degradation. Transient expression of the viral tegument proteins of pp71 and UL26 reduced NICD1 and Jag1 protein levels endogenously and exogenously. Given the critical role of Notch signaling in NPC growth and differentiation, these findings reveal important mechanisms by which HCMV disturbs neural cell development<jats:italic>in vitro</jats:italic>. Similar events<jats:italic>in vivo</jats:italic>may be associated with HCMV-mediated neuropathogenesis during congenital infection in the fetal brain.</jats:p><jats:p><jats:bold>IMPORTANCE</jats:bold>Congenital human cytomegalovirus (HCMV) infection is the leading cause of birth defects that primarily manifest as neurological disabilities. Neural progenitor cells (NPCs), key players in fetal brain development, are the most susceptible cell type for HCMV infection in the fetal brain. Studies have shown that NPCs are fully permissive for HCMV infection, which causes neural cell loss and premature differentiation, thereby perturbing NPC fate. Elucidation of virus-host interactions that govern NPC proliferation and differentiation is critical to understanding neuropathogenesis. The Notch signaling pathway is critical for maintaining stem cell status and functions as a switch for differentiation of NPCs. Our investigation into the impact of HCMV infection on this pathway revealed that HCMV dysregulates Notch signaling by altering expression of the Notch ligand Jag1, Notch1, and its active effector in NPCs. These results suggest a mechanism for the neuropathogenesis induced by HCMV infection that includes altered NPC differentiation and proliferation.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bonnaud2015,

title = {Borna Disease Virus Phosphoprotein Modulates Epigenetic Signaling in Neurons To Control Viral Replication},

author = {Emilie M. Bonnaud and Marion Szelechowski and Alexandre Bétourné and Charlotte Foret and Anne Thouard and Daniel Gonzalez-Dunia and Cécile E. Malnou},

editor = {S. R. Ross},

doi = {10.1128/jvi.00454-15},

issn = {1098-5514},

year  = {2015},

date = {2015-06-00},

urldate = {2015-06-00},

journal = {J Virol},

volume = {89},

number = {11},

pages = {5996--6008},

publisher = {American Society for Microbiology},

abstract = {<jats:title>ABSTRACT</jats:title>

          <jats:p>Understanding the modalities of interaction of neurotropic viruses with their target cells represents a major challenge that may improve our knowledge of many human neurological disorders for which viral origin is suspected. Borna disease virus (BDV) represents an ideal model to analyze the molecular mechanisms of viral persistence in neurons and its consequences for neuronal homeostasis. It is now established that BDV ensures its long-term maintenance in infected cells through a stable interaction of viral components with the host cell chromatin, in particular, with core histones. This has led to our hypothesis that such an interaction may trigger epigenetic changes in the host cell. Here, we focused on histone acetylation, which plays key roles in epigenetic regulation of gene expression, notably for neurons. We performed a comparative analysis of histone acetylation patterns of neurons infected or not infected by BDV, which revealed that infection decreases histone acetylation on selected lysine residues. We showed that the BDV phosphoprotein (P) is responsible for these perturbations, even when it is expressed alone independently of the viral context, and that this action depends on its phosphorylation by protein kinase C. We also demonstrated that BDV P inhibits cellular histone acetyltransferase activities. Finally, by pharmacologically manipulating cellular acetylation levels, we observed that inhibiting cellular acetyl transferases reduces viral replication in cell culture. Our findings reveal that manipulation of cellular epigenetics by BDV could be a means to modulate viral replication and thus illustrate a fascinating example of virus-host cell interaction.</jats:p>

          <jats:p>

            <jats:bold>IMPORTANCE</jats:bold>

            Persistent DNA viruses often subvert the mechanisms that regulate cellular chromatin dynamics, thereby benefitting from the resulting epigenetic changes to create a favorable milieu for their latent and persistent states. Here, we reasoned that Borna disease virus (BDV), the only RNA virus known to durably persist in the nucleus of infected cells, notably neurons, might employ a similar mechanism. In this study, we uncovered a novel modality of virus-cell interaction in which BDV phosphoprotein inhibits cellular histone acetylation by interfering with histone acetyltransferase activities. Manipulation of cellular histone acetylation is accompanied by a modulation of viral replication, revealing a perfect adaptation of this “ancient” virus to its host that may favor neuronal persistence and limit cellular damage.

          </jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Scordel2015b,

title = {Borna Disease Virus Phosphoprotein Impairs the Developmental Program Controlling Neurogenesis and Reduces Human GABAergic Neurogenesis},

author = {Chloé Scordel and Alexandra Huttin and Marielle Cochet-Bernoin and Marion Szelechowski and Aurélie Poulet and Jennifer Richardson and Alexandra Benchoua and Daniel Gonzalez-Dunia and Marc Eloit and Muriel Coulpier},

editor = {Martin Schwemmle},

doi = {10.1371/journal.ppat.1004859},

issn = {1553-7374},

year  = {2015},

date = {2015-04-29},

journal = {PLoS Pathog},

volume = {11},

number = {4},

publisher = {Public Library of Science (PLoS)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pendaries2015,

title = {In a three-dimensional reconstructed human epidermis filaggrin-2 is essential for proper cornification.},

author = {Pendaries, V and Le Lamer, M and Cau, L and Hansmann, B and Malaisse, J and Kezic, S and Serre, G and Simon, M},

doi = {10.1038/cddis.2015.29},

issn = {2041-4889 (Electronic)},

year  = {2015},

date = {2015-02-01},

journal = {Cell death & disease},

volume = {6},

number = {2},

pages = {e1656},

abstract = {Atopic dermatitis is a chronic inflammatory skin disease with defects in the epidermal barrier. In a cohort of African-American children, a FLG2 nonsense mutation has been associated with the disease. In the epidermis of European patients, the expression of filaggrin-2, the filaggrin-related protein encoded by FLG2, is decreased. To describe the function of filaggrin-2 and evaluate the impact of its deficiency, its expression was downregulated using lentivirus-mediated shRNA interference in a three-dimensional reconstructed human epidermis (RHE) model. This resulted in parakeratosis and a compact stratum corneum, presence of abnormal vesicles inside the corneocytes, increased pH and reduced amounts of free amino acids at the RHE surface, leading to increased sensitivity to UVB radiations. The expression of differentiation markers was slightly modified. However, we observed reduced proteolytic processing of corneodesmosin, hornerin and filaggrin in parallel with reduced amounts of caspase-14 and bleomycin hydrolase. Our data demonstrated that filaggrin-2 is important for a proper cornification and a functional stratum corneum. Its downregulation in atopic patients may be involved in the disease-associated epidermis impairment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}