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  1. Article ; Online: Impact of disrupted cyclic stretch in intracranial aneurysms: Insights from endothelial cell transcriptomic dataset.

    Diagbouga, Mannekomba R / Lemeille, Sylvain / Morel, Sandrine / Kwak, Brenda R

    Data in brief

    2023  Volume 52, Page(s) 110014

    Abstract: Intracranial aneurysm (IA) rupture is a common cause of hemorrhagic stroke. The treatment of unruptured IAs is a challenging decision that requires delicate risk stratification. The rate of poor clinical outcomes after surgical intervention (aneurysm ... ...

    Abstract Intracranial aneurysm (IA) rupture is a common cause of hemorrhagic stroke. The treatment of unruptured IAs is a challenging decision that requires delicate risk stratification. The rate of poor clinical outcomes after surgical intervention (aneurysm clipping) or endovascular coiling remains elevated (6.7% and 4.8%, respectively), and they do not provide an absolute guarantee to prevent IA growth and rupture. Currently, there is no pharmaceutical treatment to cure or stabilize IAs. Improving the current or developing new treatments for IA disease would require a better understanding of the cellular and molecular mechanisms occurring in the different stages of the disease. Hemodynamic forces play a critical role in IA disease. While the role of wall shear stress in IAs is well-established, the influence of cyclic circumferential stretch (CCS) still needs clarification. IAs are generally characterized by a lack of CCS. In this investigation, we sought to understand the effect of aneurysmal CCS on endothelial cell (EC) function and its potential significance in IA disease, hypothesizing that CCS can influence IA wall remodelling. RNA-seq data were generated from human umbilical vein ECs (HUVECs) exposed to physiological (6%) or aneurysmal CCS (static). We performed differential gene expression and pathway enrichment analysis. Additionally, we highlighted cell junction gene expression between static and 6% CCS to contribute to the debate about how cell junctions affect endothelium stability and integrity. Researchers in the vascular biology field may benefit from this transcriptomic profile to understand the effect of mechanical stretch on EC biology and its potential significance in vascular disease development.
    Language English
    Publishing date 2023-12-28
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2786545-9
    ISSN 2352-3409 ; 2352-3409
    ISSN (online) 2352-3409
    ISSN 2352-3409
    DOI 10.1016/j.dib.2023.110014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Refined innate plasma signature after rVSVΔG-ZEBOV-GP immunization is shared among adult cohorts in Europe and North America.

    Martinez-Murillo, Paola Andrea / Huttner, Angela / Lemeille, Sylvain / Medaglini, Donata / Ottenhoff, Tom H M / Harandi, Ali M / Didierlaurent, Arnaud M / Siegrist, Claire-Anne

    Frontiers in immunology

    2024  Volume 14, Page(s) 1279003

    Abstract: Background: During the last decade Ebola virus has caused several outbreaks in Africa. The recombinant vesicular stomatitis virus-vectored Zaire Ebola (rVSVΔG-ZEBOV-GP) vaccine has proved safe and immunogenic but is reactogenic. We previously identified ...

    Abstract Background: During the last decade Ebola virus has caused several outbreaks in Africa. The recombinant vesicular stomatitis virus-vectored Zaire Ebola (rVSVΔG-ZEBOV-GP) vaccine has proved safe and immunogenic but is reactogenic. We previously identified the first innate plasma signature response after vaccination in Geneva as composed of five monocyte-related biomarkers peaking at day 1 post-immunization that correlates with adverse events, biological outcomes (haematological changes and viremia) and antibody titers. In this follow-up study, we sought to identify additional biomarkers in the same Geneva cohort and validate those identified markers in a US cohort.
    Methods: Additional biomarkers were identified using multiplexed protein biomarker platform O-link and confirmed by Luminex. Principal component analysis (PCA) evaluated if these markers could explain a higher variability of the vaccine response (and thereby refined the initial signature). Multivariable and linear regression models evaluated the correlations of the main components with adverse events, biological outcomes, and antibody titers. External validation of the refined signature was conducted in a second cohort of US vaccinees (n=142).
    Results: Eleven additional biomarkers peaked at day 1 post-immunization: MCP2, MCP3, MCP4, CXCL10, OSM, CX3CL1, MCSF, CXCL11, TRAIL, RANKL and IL15. PCA analysis retained three principal components (PC) that accounted for 79% of the vaccine response variability. PC1 and PC2 were very robust and had different biomarkers that contributed to their variability. PC1 better discriminated different doses, better defined the risk of fever and myalgia, while PC2 better defined the risk of headache. We also found new biomarkers that correlated with reactogenicity, including transient arthritis (MCP-2, CXCL10, CXCL11, CX3CL1, MCSF, IL-15, OSM). Several innate biomarkers are associated with antibody levels one and six months after vaccination. Refined PC1 correlated strongly in both data sets (Geneva: r = 0.97, P < 0.001; US: r = 0.99, P< 0.001).
    Conclusion: Eleven additional biomarkers refined the previously found 5-biomarker Geneva signature. The refined signature better discriminated between different doses, was strongly associated with the risk of adverse events and with antibody responses and was validated in a separate cohort.
    MeSH term(s) Adult ; Humans ; Follow-Up Studies ; Antibodies, Viral ; Ebola Vaccines ; Vaccination ; Europe ; North America ; Democratic Republic of the Congo ; Biomarkers
    Chemical Substances Antibodies, Viral ; Ebola Vaccines ; Biomarkers
    Language English
    Publishing date 2024-01-03
    Publishing country Switzerland
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1279003
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  3. Article: Genetic knockout of

    Roussel-Gervais, Audrey / Sgroi, Stéphanie / Cambet, Yves / Lemeille, Sylvain / Seredenina, Tamara / Krause, Karl-Heinz / Jaquet, Vincent

    Frontiers in cellular neuroscience

    2023  Volume 17, Page(s) 1289966

    Abstract: The tropomyosin receptor kinase B (TrkB) is encoded by ... ...

    Abstract The tropomyosin receptor kinase B (TrkB) is encoded by the
    Language English
    Publishing date 2023-12-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2023.1289966
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Immune response of polarized cystic fibrosis airway epithelial cells infected with Influenza A virus.

    Sofoluwe, Aderonke / Zoso, Alice / Bacchetta, Marc / Lemeille, Sylvain / Chanson, Marc

    Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

    2020  Volume 20, Issue 4, Page(s) 655–663

    Abstract: Background: Cystic fibrosis (CF), a genetic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, is characterized by dysfunction of the immune response in the airway epithelium that leads to prolonged ... ...

    Abstract Background: Cystic fibrosis (CF), a genetic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, is characterized by dysfunction of the immune response in the airway epithelium that leads to prolonged infection, colonization and exacerbated inflammation. In this study, we determined the gene expression profile of airway epithelial cells knockdown for CFTR (CFTR KD) in response to bacterial and viral challenges.
    Methods: In a first approach, polarized CFTR KD and their control counterpart (CFTR CTL) cells were stimulated with P. aeruginosa-derived virulence factor flagellin. Next, we developed a model of Influenza A virus (IAV) infection in CTL and CFTR KD polarized cells. mRNA was collected for transcriptome analysis.
    Results: Beside the expected pro-inflammatory response, Gene Set Enrichment Analysis highlighted key molecular pathways and players involved in IAV and anti-viral interferon signaling. Although IAV replication was similar in both cell types, multiplex gene expression analysis revealed changes of key immune genes dependent on time of infection that were found to be CFTR-dependent and/or IAV-dependent. Interferons are key signaling proteins/cytokines in the antibacterial and antiviral response. To evaluate their impact on the altered gene expression profile in CFTR responses to pathogens, we measured transcriptome changes after exposure to Type I-, Type II- and Type III-interferons.
    Conclusions: Our findings reveal target genes in understanding the defective immune response in the CF airway epithelium in the context of viral infection. Information provided in this study would be useful to understand the dysfunctional immune response of the CF airway epithelium during infection.
    MeSH term(s) Cells, Cultured ; Cystic Fibrosis/genetics ; Cystic Fibrosis/immunology ; Epithelial Cells/immunology ; Epithelial Cells/virology ; Humans ; Immunity/genetics ; Influenza A virus ; Respiratory Mucosa/cytology
    Language English
    Publishing date 2020-08-29
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2084724-5
    ISSN 1873-5010 ; 1569-1993
    ISSN (online) 1873-5010
    ISSN 1569-1993
    DOI 10.1016/j.jcf.2020.08.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Transcriptomic Analysis of

    Roth, Myriam / Jaquet, Vincent / Lemeille, Sylvain / Bonetti, Eve-Julie / Cambet, Yves / François, Patrice / Krause, Karl-Heinz

    Antioxidants (Basel, Switzerland)

    2022  Volume 11, Issue 4

    Abstract: Hydrogen peroxide ( ... ...

    Abstract Hydrogen peroxide (H
    Language English
    Publishing date 2022-03-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox11040655
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Intracellular IL-1 Receptor Antagonist Isoform 1 Released from Keratinocytes upon Cell Death Acts as an Inhibitor for the Alarmin IL-1α.

    Martin, Praxedis / Palmer, Gaby / Rodriguez, Emiliana / Palomo, Jennifer / Lemeille, Sylvain / Goldstein, Jérémie / Gabay, Cem

    Journal of immunology (Baltimore, Md. : 1950)

    2020  Volume 204, Issue 4, Page(s) 967–979

    Abstract: The inflammatory effects of IL-1α/β are controlled by IL-1R antagonist (IL-1Ra). One IL-1Ra isoform is secreted, whereas three other isoforms (intracellular IL-1Ra [icIL-1Ra] 1, 2, and 3) are supposed to remain intracellular because of the absence of a ... ...

    Abstract The inflammatory effects of IL-1α/β are controlled by IL-1R antagonist (IL-1Ra). One IL-1Ra isoform is secreted, whereas three other isoforms (intracellular IL-1Ra [icIL-1Ra] 1, 2, and 3) are supposed to remain intracellular because of the absence of a signal peptide. In contrast to the well-characterized function of the secreted isoform, the biological role of the intracellular isoforms remains largely unclear. icIL-1Ra1 represents the major isoform in keratinocytes. We created icIL-1Ra1
    MeSH term(s) Alarmins/antagonists & inhibitors ; Alarmins/immunology ; Alarmins/metabolism ; Animals ; Apoptosis/immunology ; Disease Models, Animal ; Female ; Humans ; Imiquimod/immunology ; Interleukin 1 Receptor Antagonist Protein/immunology ; Interleukin 1 Receptor Antagonist Protein/metabolism ; Interleukin-1alpha/antagonists & inhibitors ; Interleukin-1alpha/immunology ; Interleukin-1alpha/metabolism ; Keratinocytes/metabolism ; Male ; Mice ; Mice, Knockout ; Protein Isoforms/immunology ; Protein Isoforms/metabolism ; Psoriasis/diagnosis ; Psoriasis/immunology ; Psoriasis/pathology ; Severity of Illness Index ; Signal Transduction/immunology ; Skin/cytology ; Skin/immunology ; Skin/pathology
    Chemical Substances Alarmins ; Il1a protein, mouse ; Il1rn protein, mouse ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-1alpha ; Protein Isoforms ; Imiquimod (P1QW714R7M)
    Language English
    Publishing date 2020-01-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1901074
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  7. Article ; Online: Human fetal mesoangioblasts reveal tissue-dependent transcriptional signatures.

    Ronzoni, Flavio L / Lemeille, Sylvain / Kuzyakiv, Rostyslav / Sampaolesi, Maurilio / Jaconi, Marisa E

    Stem cells translational medicine

    2020  Volume 9, Issue 5, Page(s) 575–589

    Abstract: Mesoangioblasts (MABs) derived from adult skeletal muscles are well-studied adult stem/progenitor cells that already entered clinical trials for muscle regeneration in genetic diseases; however, the transcriptional identity of human fetal MABs (fMABs) ... ...

    Abstract Mesoangioblasts (MABs) derived from adult skeletal muscles are well-studied adult stem/progenitor cells that already entered clinical trials for muscle regeneration in genetic diseases; however, the transcriptional identity of human fetal MABs (fMABs) remains largely unknown. Herein we analyzed the transcriptome of MABs isolated according to canonical markers from fetal atrium, ventricle, aorta, and skeletal muscles (from 9.5 to 13 weeks of age) to uncover specific gene signatures correlating with their peculiar myogenic differentiation properties inherent to their tissue of origin. RNA-seq analysis revealed for the first time that human MABs from fetal aorta, cardiac (atrial and ventricular), and skeletal muscles display subsets of differentially expressed genes likely representing distinct expression signatures indicative of their original tissue. Identified GO biological processes and KEGG pathways likely account for their distinct differentiation outcomes and provide a set of critical genes possibly predicting future specific differentiation outcomes. This study reveals novel information regarding the potential of human fMABs that may help to improve specific differentiation outcomes relevant for therapeutic muscle regeneration.
    MeSH term(s) Cells, Cultured ; Humans ; Muscle Development/physiology ; Muscle, Skeletal/metabolism
    Language English
    Publishing date 2020-01-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2642270-0
    ISSN 2157-6580 ; 2157-6564
    ISSN (online) 2157-6580
    ISSN 2157-6564
    DOI 10.1002/sctm.19-0209
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  8. Article ; Online: Intratumoral CpG-B Promotes Antitumoral Neutrophil, cDC, and T-cell Cooperation without Reprograming Tolerogenic pDC.

    Humbert, Marion / Guery, Leslie / Brighouse, Dale / Lemeille, Sylvain / Hugues, Stephanie

    Cancer research

    2018  Volume 78, Issue 12, Page(s) 3280–3292

    Abstract: Cancer immunotherapies utilize distinct mechanisms to harness the power of the immune system to eradicate cancer cells. Therapeutic vaccines, aimed at inducing active immune responses against an existing cancer, are highly dependent on the immunological ... ...

    Abstract Cancer immunotherapies utilize distinct mechanisms to harness the power of the immune system to eradicate cancer cells. Therapeutic vaccines, aimed at inducing active immune responses against an existing cancer, are highly dependent on the immunological microenvironment, where many immune cell types display high levels of plasticity and, depending on the context, promote very different immunologic outcomes. Among them, plasmacytoid dendritic cells (pDC), known to be highly immunogenic upon inflammation, are maintained in a tolerogenic state by the tumor microenvironment. Here, we report that intratumoral (i.t.) injection of established solid tumors with CpG oligonucleotides-B (CpG-B) inhibits tumor growth. Interestingly, control of tumor growth was independent of tumor-associated pDC, which remained refractory to CpG-B stimulation and whose depletion did not alter the efficacy of the treatment. Instead, tumor growth inhibition subsequent to i.t. CpG-B injection depended on the recruitment of neutrophils into the milieu, resulting in the activation of conventional dendritic cells, subsequent increased antitumor T-cell priming in draining lymph nodes, and enhanced effector T-cell infiltration in the tumor microenvironment. These results reinforce the concept that i.t. delivery of TLR9 agonists alters the tumor microenvironment by improving the antitumor activity of both innate and adaptive immune cells.
    MeSH term(s) Adjuvants, Immunologic/administration & dosage ; Animals ; Antigens, Neoplasm/administration & dosage ; Antigens, Neoplasm/immunology ; Cancer Vaccines/administration & dosage ; Cancer Vaccines/immunology ; Cell Communication/drug effects ; Cell Communication/immunology ; Cell Line, Tumor/transplantation ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Disease Models, Animal ; Histocompatibility Antigens Class II/administration & dosage ; Histocompatibility Antigens Class II/immunology ; Humans ; Immune Tolerance/drug effects ; Immunotherapy/methods ; Injections, Intralesional ; Lymphocyte Activation/drug effects ; Mice ; Mice, Inbred C57BL ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/therapy ; Neutrophils/drug effects ; Neutrophils/immunology ; Oligodeoxyribonucleotides/administration & dosage ; Ovalbumin/administration & dosage ; Ovalbumin/immunology ; Peptide Fragments/administration & dosage ; Peptide Fragments/immunology ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; Toll-Like Receptor 9/agonists ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/immunology
    Chemical Substances Adjuvants, Immunologic ; Antigens, Neoplasm ; Cancer Vaccines ; CpG-B 2006 ; Histocompatibility Antigens Class II ; OVA 323-339 ; Oligodeoxyribonucleotides ; Peptide Fragments ; TLR9 protein, human ; Toll-Like Receptor 9 ; Ovalbumin (9006-59-1)
    Language English
    Publishing date 2018-03-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-17-2549
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  9. Article: Effects of Low and High Aneurysmal Wall Shear Stress on Endothelial Cell Behavior: Differences and Similarities.

    Morel, Sandrine / Schilling, Sabine / Diagbouga, Mannekomba R / Delucchi, Matteo / Bochaton-Piallat, Marie-Luce / Lemeille, Sylvain / Hirsch, Sven / Kwak, Brenda R

    Frontiers in physiology

    2021  Volume 12, Page(s) 727338

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2021-10-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2021.727338
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  10. Article ; Online: Persistence of self-reactive CD8+ T cells in the CNS requires TOX-dependent chromatin remodeling.

    Page, Nicolas / Lemeille, Sylvain / Vincenti, Ilena / Klimek, Bogna / Mariotte, Alexandre / Wagner, Ingrid / Di Liberto, Giovanni / Kaye, Jonathan / Merkler, Doron

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 1009

    Abstract: Self-reactive ... ...

    Abstract Self-reactive CD8
    MeSH term(s) Animals ; Autoimmunity/immunology ; CD8-Positive T-Lymphocytes/immunology ; Central Nervous System/metabolism ; Chromatin Assembly and Disassembly ; Female ; Gene Expression Regulation ; Immunologic Memory ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout
    Language English
    Publishing date 2021-02-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-21109-3
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