Publications

@article{pmid27924814,

title = {Mature IgM-expressing plasma cells sense antigen and develop competence for cytokine production upon antigenic challenge},

author = {Pascal Blanc and Ludovic Moro-Sibilot and Lucas Barthly and Ferdinand Jagot and Sébastien This and Simon de Bernard and Laurent Buffat and Sébastien Dussurgey and Renaud Colisson and Elias Hobeika and Thierry Fest and Morgan Taillardet and Olivier Thaunat and Antoine Sicard and Paul Mondière and Laurent Genestier and Stephen L Nutt and Thierry Defrance},

doi = {10.1038/ncomms13600},

issn = {2041-1723},

year  = {2016},

date = {2016-12-01},

urldate = {2016-12-01},

journal = {Nat Commun},

volume = {7},

pages = {13600},

abstract = {Dogma holds that plasma cells, as opposed to B cells, cannot bind antigen because they have switched from expression of membrane-bound immunoglobulins (Ig) that constitute the B-cell receptor (BCR) to production of the secreted form of immunoglobulins. Here we compare the phenotypical and functional attributes of plasma cells generated by the T-cell-dependent and T-cell-independent forms of the hapten NP. We show that the nature of the secreted Ig isotype, rather than the chemical structure of the immunizing antigen, defines two functionally distinct populations of plasma cells. Fully mature IgM-expressing plasma cells resident in the bone marrow retain expression of a functional BCR, whereas their IgG counterparts do not. Antigen boost modifies the gene expression profile of IgM plasma cells and initiates a cytokine production program, characterized by upregulation of CCL5 and IL-10. Our results demonstrate that IgM-expressing plasma cells can sense antigen and acquire competence for cytokine production upon antigenic challenge.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27883012,

title = {Immune signatures of protective spleen memory CD8 T cells},

author = {Lilia Brinza and Sophia Djebali and Martine Tomkowiak and Julien Mafille and Céline Loiseau and Pierre-Emmanuel Jouve and Simon de Bernard and Laurent Buffat and Bruno Lina and Michèle Ottmann and Manuel Rosa-Calatrava and Stéphane Schicklin and Nathalie Bonnefoy and Grégoire Lauvau and Morgan Grau and Mélanie Wencker and Christophe Arpin and Thierry Walzer and Yann Leverrier and Jacqueline Marvel},

doi = {10.1038/srep37651},

issn = {2045-2322},

year  = {2016},

date = {2016-11-01},

urldate = {2016-11-01},

journal = {Sci Rep},

volume = {6},

pages = {37651},

abstract = {Memory CD8 T lymphocyte populations are remarkably heterogeneous and differ in their ability to protect the host. In order to identify the whole range of qualities uniquely associated with protective memory cells we compared the gene expression signatures of two qualities of memory CD8 T cells sharing the same antigenic-specificity: protective (Influenza-induced, Flu-TM) and non-protective (peptide-induced, TIM) spleen memory CD8 T cells. Although Flu-TM and TIM express classical phenotypic memory markers and are polyfunctional, only Flu-TM protects against a lethal viral challenge. Protective memory CD8 T cells express a unique set of genes involved in migration and survival that correlate with their unique capacity to rapidly migrate within the infected lung parenchyma in response to influenza infection. We also enlighten a new set of poised genes expressed by protective cells that is strongly enriched in cytokines and chemokines such as Ccl1, Ccl9 and Gm-csf. CCL1 and GM-CSF genes are also poised in human memory CD8 T cells. These immune signatures are also induced by two other pathogens (vaccinia virus and Listeria monocytogenes). The immune signatures associated with immune protection were identified on circulating cells, i.e. those that are easily accessible for immuno-monitoring and could help predict vaccines efficacy.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27069116,

title = {CD1d-restricted peripheral T cell lymphoma in mice and humans},

author = {Emmanuel Bachy and Mirjam Urb and Shilpi Chandra and Rémy Robinot and Gabriel Bricard and Simon de Bernard and Alexandra Traverse-Glehen and Sophie Gazzo and Olivier Blond and Archana Khurana and Lucile Baseggio and Tayla Heavican and Martine Ffrench and Giuliano Crispatzu and Paul Mondière and Alexandra Schrader and Morgan Taillardet and Olivier Thaunat and Nadine Martin and Stéphane Dalle and Magali Le Garff-Tavernier and Gilles Salles and Joel Lachuer and Olivier Hermine and Vahid Asnafi and Mikael Roussel and Thierry Lamy and Marco Herling and Javeed Iqbal and Laurent Buffat and Patrice N Marche and Philippe Gaulard and Mitchell Kronenberg and Thierry Defrance and Laurent Genestier},

doi = {10.1084/jem.20150794},

issn = {1540-9538},

year  = {2016},

date = {2016-05-01},

urldate = {2016-05-01},

journal = {J Exp Med},

volume = {213},

number = {5},

pages = {841--857},

abstract = {Peripheral T cell lymphomas (PTCLs) are a heterogeneous entity of neoplasms with poor prognosis, lack of effective therapies, and a largely unknown pathophysiology. Identifying the mechanism of lymphomagenesis and cell-of-origin from which PTCLs arise is crucial for the development of efficient treatment strategies. In addition to the well-described thymic lymphomas, we found that p53-deficient mice also developed mature PTCLs that did not originate from conventional T cells but from CD1d-restricted NKT cells. PTCLs showed phenotypic features of activated NKT cells, such as PD-1 up-regulation and loss of NK1.1 expression. Injections of heat-killed Streptococcus pneumonia, known to express glycolipid antigens activating NKT cells, increased the incidence of these PTCLs, whereas Escherichia coli injection did not. Gene expression profile analyses indicated a significant down-regulation of genes in the TCR signaling pathway in PTCL, a common feature of chronically activated T cells. Targeting TCR signaling pathway in lymphoma cells, either with cyclosporine A or anti-CD1d blocking antibody, prolonged mice survival. Importantly, we identified human CD1d-restricted lymphoma cells within Vδ1 TCR-expressing PTCL. These results define a new subtype of PTCL and pave the way for the development of blocking anti-CD1d antibody for therapeutic purposes in humans.},

keywords = {cytometry},

pubstate = {published},

tppubtype = {article}

}

@article{pmid26503444,

title = {Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection},

author = {Mary J van Helden and Steven Goossens and Cécile Daussy and Anne-Laure Mathieu and Fabrice Faure and Antoine Marçais and Niels Vandamme and Natalie Farla and Katia Mayol and Sébastien Viel and Sophie Degouve and Emilie Debien and Eve Seuntjens and Andrea Conidi and Julie Chaix and Philippe Mangeot and Simon de Bernard and Laurent Buffat and Jody J Haigh and Danny Huylebroeck and Bart N Lambrecht and Geert Berx and Thierry Walzer},

doi = {10.1084/jem.20150809},

issn = {1540-9538},

year  = {2015},

date = {2015-11-01},

urldate = {2015-11-01},

journal = {J Exp Med},

volume = {212},

number = {12},

pages = {2015--2025},

abstract = {Natural killer (NK) cell maturation is a tightly controlled process that endows NK cells with functional competence and the capacity to recognize target cells. Here, we found that the transcription factor (TF) Zeb2 was the most highly induced TF during NK cell maturation. Zeb2 is known to control epithelial to mesenchymal transition, but its role in immune cells is mostly undefined. Targeted deletion of Zeb2 resulted in impaired NK cell maturation, survival, and exit from the bone marrow. NK cell function was preserved, but mice lacking Zeb2 in NK cells were more susceptible to B16 melanoma lung metastases. Reciprocally, ectopic expression of Zeb2 resulted in a higher frequency of mature NK cells in all organs. Moreover, the immature phenotype of Zeb2(-/-) NK cells closely resembled that of Tbx21(-/-) NK cells. This was caused by both a dependence of Zeb2 expression on T-bet and a probable cooperation of these factors in gene regulation. Transgenic expression of Zeb2 in Tbx21(-/-) NK cells partially restored a normal maturation, establishing that timely induction of Zeb2 by T-bet is an essential event during NK cell differentiation. Finally, this novel transcriptional cascade could also operate in human as T-bet and Zeb2 are similarly regulated in mouse and human NK cells.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25029475,

title = {A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis},

author = {Yasmina Bauer and John Tedrow and Simon de Bernard and Magdalena Birker-Robaczewska and Kevin F Gibson and Brenda Juan Guardela and Patrick Hess and Axel Klenk and Kathleen O Lindell and Sylvie Poirey and Bérengère Renault and Markus Rey and Edgar Weber and Oliver Nayler and Naftali Kaminski},

doi = {10.1165/rcmb.2013-0310OC},

issn = {1535-4989},

year  = {2015},

date = {2015-02-01},

urldate = {2015-02-01},

journal = {Am J Respir Cell Mol Biol},

volume = {52},

number = {2},

pages = {217--231},

abstract = {The bleomycin-induced rodent lung fibrosis model is commonly used to study mechanisms of lung fibrosis and to test potential therapeutic interventions, despite the well recognized dissimilarities to human idiopathic pulmonary fibrosis (IPF). Therefore, in this study, we sought to identify genomic commonalities between the gene expression profiles from 100 IPF lungs and 108 control lungs that were obtained from the Lung Tissue Research Consortium, and rat lungs harvested at Days 3, 7, 14, 21, 28, 42, and 56 after bleomycin instillation. Surprisingly, the highest gene expression similarity between bleomycin-treated rat and IPF lungs was observed at Day 7. At this point of maximal rat-human commonality, we identified a novel set of 12 disease-relevant translational gene markers (C6, CTHRC1, CTSE, FHL2, GAL, GREM1, LCN2, MMP7, NELL1, PCSK1, PLA2G2A, and SLC2A5) that was able to separate almost all patients with IPF from control subjects in our cohort and in two additional IPF/control cohorts (GSE10667 and GSE24206). Furthermore, in combination with diffusing capacity of carbon monoxide measurements, four members of the translational gene marker set contributed to stratify patients with IPF according to disease severity. Significantly, pirfenidone attenuated the expression change of one (CTHRC1) translational gene marker in the bleomycin-induced lung fibrosis model, in transforming growth factor-β1-treated primary human lung fibroblasts and transforming growth factor-β1-treated human epithelial A549 cells. Our results suggest that a strategy focused on rodent model-human disease commonalities may identify genes that could be used to predict the pharmacological impact of therapeutic interventions, and thus facilitate the development of novel treatments for this devastating lung disease.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25209580,

title = {Dramatic response of a BRAF V600E-mutated primary CNS histiocytic sarcoma to vemurafenib},

author = {Ahmed Idbaih and Karima Mokhtari and Jean-François Emile and Damien Galanaud and Hayat Belaid and Simon de Bernard and Neila Benameur and Vlad-Ciprian Barlog and Dimitri Psimaras and Jean Donadieu and Catherine Carpentier and Nadine Martin-Duverneuil and Julien Haroche and Loic Feuvret and Noel Zahr and Jean-Yves Delattre and Khê Hoang-Xuan},

doi = {10.1212/WNL.0000000000000880},

issn = {1526-632X},

year  = {2014},

date = {2014-10-01},

urldate = {2014-10-01},

journal = {Neurology},

volume = {83},

number = {16},

pages = {1478--1480},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24516120,

title = {T-bet and Eomes instruct the development of two distinct natural killer cell lineages in the liver and in the bone marrow},

author = {Cécile Daussy and Fabrice Faure and Katia Mayol and Sébastien Viel and Georg Gasteiger and Emily Charrier and Jacques Bienvenu and Thomas Henry and Emilie Debien and Uzma A Hasan and Jacqueline Marvel and Keigyou Yoh and Satoru Takahashi and Immo Prinz and Simon de Bernard and Laurent Buffat and Thierry Walzer},

doi = {10.1084/jem.20131560},

issn = {1540-9538},

year  = {2014},

date = {2014-03-01},

urldate = {2014-03-01},

journal = {J Exp Med},

volume = {211},

number = {3},

pages = {563--577},

abstract = {Trail(+)DX5(-)Eomes(-) natural killer (NK) cells arise in the mouse fetal liver and persist in the adult liver. Their relationships with Trail(-)DX5(+) NK cells remain controversial. We generated a novel Eomes-GFP reporter murine model to address this question. We found that Eomes(-) NK cells are not precursors of classical Eomes(+) NK cells but rather constitute a distinct lineage of innate lymphoid cells. Eomes(-) NK cells are strictly dependent on both T-bet and IL-15, similarly to NKT cells. We observed that, in the liver, expression of T-bet in progenitors represses Eomes expression and the development of Eomes(+) NK cells. Reciprocally, the bone marrow (BM) microenvironment restricts T-bet expression in developing NK cells. Ectopic expression of T-bet forces the development of Eomes(-) NK cells, demonstrating that repression of T-bet is essential for the development of Eomes(+) NK cells. Gene profile analyses show that Eomes(-) NK cells share part of their transcriptional program with NKT cells, including genes involved in liver homing and NK cell receptors. Moreover, Eomes(-) NK cells produce a broad range of cytokines, including IL-2 and TNF in vitro and in vivo, during immune responses against vaccinia virus. Thus, mutually exclusive expression of T-bet and Eomes drives the development of different NK cell lineages with complementary functions.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24422634,

title = {Retinoic acid receptor subtype-specific transcriptotypes in the early zebrafish embryo},

author = {Eric Samarut and Cyril Gaudin and Sandrine Hughes and Benjamin Gillet and Simon de Bernard and Pierre-Emmanuel Jouve and Laurent Buffat and Alexis Allot and Odile Lecompte and Liubov Berekelya and Cécile Rochette-Egly and Vincent Laudet},

doi = {10.1210/me.2013-1358},

issn = {1944-9917},

year  = {2014},

date = {2014-02-01},

urldate = {2014-02-01},

journal = {Mol Endocrinol},

volume = {28},

number = {2},

pages = {260--272},

abstract = {Retinoic acid (RA) controls many aspects of embryonic development by binding to specific receptors (retinoic acid receptors [RARs]) that regulate complex transcriptional networks. Three different RAR subtypes are present in vertebrates and play both common and specific roles in transducing RA signaling. Specific activities of each receptor subtype can be correlated with its exclusive expression pattern, whereas shared activities between different subtypes are generally assimilated to functional redundancy. However, the question remains whether some subtype-specific activity still exists in regions or organs coexpressing multiple RAR subtypes. We tackled this issue at the transcriptional level using early zebrafish embryo as a model. Using morpholino knockdown, we specifically invalidated the zebrafish endogenous RAR subtypes in an in vivo context. After building up a list of RA-responsive genes in the zebrafish gastrula through a whole-transcriptome analysis, we compared this panel of genes with those that still respond to RA in embryos lacking one or another RAR subtype. Our work reveals that RAR subtypes do not have fully redundant functions at the transcriptional level but can transduce RA signal in a subtype-specific fashion. As a result, we define RAR subtype-specific transcriptotypes that correspond to repertoires of genes activated by different RAR subtypes. Finally, we found genes of the RA pathway (cyp26a1, raraa) the regulation of which by RA is highly robust and can even resist the knockdown of all RARs. This suggests that RA-responsive genes are differentially sensitive to alterations in the RA pathway and, in particular, cyp26a1 and raraa are under a high pressure to maintain signaling integrity.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25566510,

title = {Granulomatous response to Coxiella burnetii, the agent of Q fever: the lessons from gene expression analysis},

author = {Delphine Faugaret and Amira Ben Amara and Julie Alingrin and Aurélie Daumas and Amélie Delaby and Catherine Lépolard and Didier Raoult and Julien Textoris and Jean-Louis Mège},

doi = {10.3389/fcimb.2014.00172},

issn = {2235-2988},

year  = {2014},

date = {2014-01-01},

urldate = {2014-01-01},

journal = {Front Cell Infect Microbiol},

volume = {4},

pages = {172},

abstract = {The formation of granulomas is associated with the resolution of Q fever, a zoonosis due to Coxiella burnetii; however the molecular mechanisms of granuloma formation remain poorly understood. We generated human granulomas with peripheral blood mononuclear cells (PBMCs) and beads coated with C. burnetii, using BCG extracts as controls. A microarray analysis showed dramatic changes in gene expression in granuloma cells of which more than 50% were commonly modulated genes in response to C. burnetii and BCG. They included M1-related genes and genes related to chemotaxis. The inhibition of the chemokines, CCL2 and CCL5, directly interfered with granuloma formation. C. burnetii granulomas also expressed a specific transcriptional profile that was essentially enriched in genes associated with type I interferon response. Our results showed that granuloma formation is associated with a core of transcriptional response based on inflammatory genes. The specific granulomatous response to C. burnetii is characterized by the activation of type 1 interferon pathway.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23840433,

title = {Differentially expressed androgen-regulated genes in androgen-sensitive tissues reveal potential biomarkers of early prostate cancer},

author = {Dogus Murat Altintas and Nathalie Allioli and Myriam Decaussin and Simon de Bernard and Alain Ruffion and Jacques Samarut and Virginie Vlaeminck-Guillem},

doi = {10.1371/journal.pone.0066278},

issn = {1932-6203},

year  = {2013},

date = {2013-01-01},

urldate = {2013-01-01},

journal = {PLoS One},

volume = {8},

number = {6},

pages = {e66278},

abstract = {BACKGROUND: Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa) among androgen-regulated genes (ARG) and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely) give rise to cancer.



METHODS: ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens) using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1).



RESULTS AND DISCUSSION: By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91) and DLX1 (0.94).



CONCLUSIONS: We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could be complementary to known genes overexpressed in PCa and included along with them in multiplex diagnostic tools.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24039440,

title = {A new Vitreoscilla filiformis extract grown on spa water-enriched medium activates endogenous cutaneous antioxidant and antimicrobial defenses through a potential Toll-like receptor 2/protein kinase C, zeta transduction pathway},

author = {Yann F Mahe and Marie-Jesus Perez and Charlotte Tacheau and Chantal Fanchon and Richard Martin and Françoise Rousset and Sophie Seite},

doi = {10.2147/CCID.S47324},

issn = {1178-7015},

year  = {2013},

date = {2013-01-01},

urldate = {2013-01-01},

journal = {Clin Cosmet Investig Dermatol},

volume = {6},

pages = {191--196},

abstract = {Vitreoscilla filiformis (VF) biomass (VFB) has been widely used in cosmetic preparations and shown to modulate the major inducible free-radical scavenger mitochondrial superoxide dismutase in skin cells. By adding La Roche-Posay (LRP) thermal spring water to the VF culture medium, we obtained a biomass (LRP-VFB) with a similar mitochondrial superoxide dismutase activation capacity to VF. Also, the new biomass more powerfully stimulated mRNA expression and antimicrobial peptides in reconstructed epidermis. Interestingly, a predictive computer model that analyzed transducing events within skin epidermal cells suggested that this protective activity may involve the Toll-like receptor 2/protein kinase C, zeta transduction pathway. Protein kinase C, zeta inhibition was effectively shown to abolish VFB-induced gene stimulation and confirmed this hypothesis. This thus opens new avenues for investigation into the improvement of skin homeostatic defense in relation to the control of its physiological microbiota and innate immunity.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23071531,

title = {SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas},

author = {Ahmed Idbaih and François Ducray and Caroline Dehais and Célia Courdy and Catherine Carpentier and Simon de Bernard and Emmanuelle Uro-Coste and Karima Mokhtari and Anne Jouvet and Jérôme Honnorat and Olivier Chinot and Carole Ramirez and Patrick Beauchesne and Alexandra Benouaich-Amiel and Joël Godard and Sandrine Eimer and Fabrice Parker and Emmanuelle Lechapt-Zalcman and Philippe Colin and Delphine Loussouarn and Thierry Faillot and Phong Dam-Hieu and Selma Elouadhani-Hamdi and Luc Bauchet and Olivier Langlois and Caroline Le Guerinel and Denys Fontaine and Elodie Vauleon and Philippe Menei and Marie Janette Motsuo Fotso and Christine Desenclos and Pierre Verrelle and François Ghiringhelli and Georges Noel and François Labrousse and Antoine Carpentier and Frédéric Dhermain and Jean-Yves Delattre and Dominique Figarella-Branger},

doi = {10.1371/journal.pone.0045950},

issn = {1932-6203},

year  = {2012},

date = {2012-01-01},

urldate = {2012-01-01},

journal = {PLoS One},

volume = {7},

number = {10},

pages = {e45950},

abstract = {Anaplastic oligodendrogliomas (AOD) are rare glial tumors in adults with relative homogeneous clinical, radiological and histological features at the time of diagnosis but dramatically various clinical courses. Studies have identified several molecular abnormalities with clinical or biological relevance to AOD (e.g. t(1;19)(q10;p10), IDH1, IDH2, CIC and FUBP1 mutations).To better characterize the clinical and biological behavior of this tumor type, the creation of a national multicentric network, named "Prise en charge des OLigodendrogliomes Anaplasiques (POLA)," has been supported by the Institut National du Cancer (InCA). Newly diagnosed and centrally validated AOD patients and their related biological material (tumor and blood samples) were prospectively included in the POLA clinical database and tissue bank, respectively.At the molecular level, we have conducted a high-resolution single nucleotide polymorphism array analysis, which included 83 patients. Despite a careful central pathological review, AOD have been found to exhibit heterogeneous genomic features. A total of 82% of the tumors exhibited a 1p/19q-co-deletion, while 18% harbor a distinct chromosome pattern. Novel focal abnormalities, including homozygously deleted, amplified and disrupted regions, have been identified. Recurring copy neutral losses of heterozygosity (CNLOH) inducing the modulation of gene expression have also been discovered. CNLOH in the CDKN2A locus was associated with protein silencing in 1/3 of the cases. In addition, FUBP1 homozygous deletion was detected in one case suggesting a putative tumor suppressor role of FUBP1 in AOD.Our study showed that the genomic and pathological analyses of AOD are synergistic in detecting relevant clinical and biological subgroups of AOD.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}