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2. Integrated analysis of whole blood oxylipin and cytokine responses after bacterial, viral, and T cell stimulation reveals new immune networks

Author

Abel, Laurent, Alcover, Andres, Aschard, Hugues, Bousso, Philippe, Bourke, Nollaig, Brodin, Petter, Bruhns, Pierre, Cerf-Bensussan, Nadine, Cumano, Ana, D’Enfert, Christophe, Deriano, Ludovic, Dillies, Marie-Agnès, Di Santo, James, Eberl, Gérard, Enninga, Jost, Fellay, Jacques, Gomperts-Boneca, Ivo, Hasan, Milena, Hedestam, Gunilla Karlsson, Hercberg, Serge, Ingersoll, Molly A., Lantz, Olivier, Kenny, Rose Anne, Ménager, Mickaël, Mouquet, Hugo, O'Farrelly, Cliona, Patin, Etienne, Pellegrini, Sandra, Rausell, Antonio, Rieux-Laucat, Frédéric, Rogge, Lars, Fontes, Magnus, Sakuntabhai, Anavaj, Schwartz, Olivier, Schwikowski, Benno, Shorte, Spencer, Tangy, Frédéric, Toubert, Antoine, Touvier, Mathilde, Ungeheuer, Marie-Noëlle, Zimmer, Christophe, Albert, Matthew L., Duffy, Darragh, Quintana-Murci, Lluis, Villain, Etienne, Chanson, Aurélie, Mainka, Malwina, Kampschulte, Nadja, Le Faouder, Pauline, Bertrand-Michel, Justine, Brandolini-Bunlon, Marion, Charbit, Bruno, Musvosvi, Munyaradzi, Bilek, Nicole, Scriba, Thomas J., Schebb, Nils Helge, and Gladine, Cécile

Published
2023
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3. Loss of the intracellular enzyme QPCTL limits chemokine function and reshapes myeloid infiltration to augment tumor immunity

Author

Barreira da Silva, Rosa, Leitao, Ricardo M., Pechuan-Jorge, Ximo, Werneke, Scott, Oeh, Jason, Javinal, Vincent, Wang, Yingyun, Phung, Wilson, Everett, Christine, Nonomiya, Jim, Arnott, David, Lu, Cheng, Hsiao, Yi-Chun, Koerber, James T., Hötzel, Isidro, Ziai, James, Modrusan, Zora, Pillow, Thomas H., Roose-Girma, Merone, Schartner, Jill M., Merchant, Mark, Rutz, Sascha, Eidenschenk, Céline, Mellman, Ira, and Albert, Matthew L.

Published
2022
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4. Early IFNβ secretion determines variable downstream IL-12p70 responses upon TLR4 activation

Author

Abel, Laurent, Alcover, Andres, Aschard, Hugues, Bousso, Philippe, Bourke, Nollaig, Brodin, Petter, Bruhns, Pierre, Cerf-Bensussan, Nadine, Cumano, Ana, Demangel, Caroline, Christophe d’Enfert, Deriano, Ludovic, Dillies, Marie-Agnès, Di Santo, James, Dromer, Françoise, Eberl, Gérard, Enninga, Jost, Fellay, Jacques, Gomperts-Boneca, Ivo, Hasan, Milena, Fontes, Magnus, Hedestam, Gunilla Karlsson, Hercberg, Serge, Ingersoll, Molly A., Kenny, Rose Anne, Lantz, Olivier, Ménager, Mickael, Michel, Frédérique, Mouquet, Hugo, O'Farrelly, Cliona, Patin, Etienne, Pellegrini, Sandra, Pol, Stanislas, Rausell, Antonio, Rieux-Laucat, Frédéric, Rogge, Lars, Sakuntabhai, Anavaj, Schwartz, Olivier, Schwikowski, Benno, Shorte, Spencer, Tangy, Frédéric, Toubert, Antoine, Touvier, Mathilde, Ungeheuer, Marie-Noëlle, Zimmer, Christophe, Albert, Matthew L., Duffy, Darragh, Quintana-Murci, Lluis, Posseme, Celine, Llibre, Alba, Charbit, Bruno, Bondet, Vincent, Rouilly, Vincent, Saint-André, Violaine, Boussier, Jeremy, Bergstedt, Jacob, Smith, Nikaïa, Townsend, Liam, Sugrue, Jamie A., Ní Cheallaigh, Clíona, Conlon, Niall, Rotival, Maxime, Kobor, Michael S., and Mottez, Estelle

Published
2022
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9. Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses

Author

Llibre, Alba, primary, Smith, Nikaïa, additional, Rouilly, Vincent, additional, Musvosvi, Munyaradzi, additional, Nemes, Elisa, additional, Posseme, Céline, additional, Mabwe, Simbarashe, additional, Charbit, Bruno, additional, Mbandi, Stanley Kimbung, additional, Filander, Elizabeth, additional, Africa, Hadn, additional, Saint-André, Violaine, additional, Bondet, Vincent, additional, Bost, Pierre, additional, Mulenga, Humphrey, additional, Bilek, Nicole, additional, Albert, Matthew L., additional, Scriba, Thomas J., additional, and Duffy, Darragh, additional

Published
2022
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10. Natural killer cell educating KIR/HLA combinations impact survival in anti-PD-L1 treated cancer patients

Author

Roe, David, primary, Rosoff, Howard, additional, Ruan, Dan Fu, additional, Khan, Zia, additional, Dogra, Pranay, additional, Carroll, Jonathan, additional, Hunkapiller, Julie, additional, Mohindra, Rajat, additional, Srivastava, Minu K., additional, Nabet, Barzin Y., additional, Chandler, G. Scott, additional, Albert, Matthew L., additional, McCarthy, Mark I., additional, Mellman, Ira, additional, Horowitz, Amir, additional, and Hammer, Christian, additional

Published
2022
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11. Variability of Primary Sjögren's Syndrome Is Driven by Interferon α and Interferon α Blood Levels Are Associated With the Class II HLA–DQ Locus

Author

Trutschel, Diana, Bost, Pierre, Mariette, Xavier, Bondet, Vincent, Llibre, Alba, Posseme, Celine, Charbit, Bruno, Thorball, Christian W., Jonsson, Roland, Lessard, Christopher J., Felten, Renaud, Ng, Wan Fai, Chatenoud, Lucienne, Dumortier, Hélène, Sibilia, Jean, Fellay, Jacques, Brokstad, Karl A., Appel, Silke, Tarn, Jessica R., Quintana‐Murci, Lluis, Mingueneau, Michael, Meyer, Nicolas, Duffy, Darragh, Schwikowski, Benno, Gottenberg, Jacques Eric, Dernis, Emmanuelle, Devauchelle‐Pensec, Valerie, Dieude, Philippe, Dubost, Jean‐Jacques, Fauchais, Anne‐Laure, Goeb, Vincent, Hachulla, Eric, Hatron, Pierre Yves, Larroche, Claire, Le Guern, Véronique, Morel, Jacques, Perdriger, Aleth, Salliot, Carinne, Rist, Stephanie, Saraux, Alain, Vittecoq, Olivier, Nocturne, Gaétane, Ravaud, Philippe, Seror, Raphaèle, Abel, Laurent, Alcover, Andres, Aschard, Hugues, Astrom, Kalla, Bousso, Philippe, Bruhns, Pierre, Cumano, Ana, Demangel, Caroline, Deriano, Ludovic, Di Santo, James, Dromer, Françoise, Eberl, Gérard, Enninga, Jost, Gelpi, Odile, GompertsBoneca, Ivo, Hasan, Milena, Hercberg, Serge, Lantz, Olivier, Leclerc, Claude, Mouquet, Hugo, Pellegrini, Sandra, Pol, Stanislas, Rausell, Antonio, Rogge, Lars, Sakuntabhai, Anavaj, Schwartz, Olivier, Shorte, Spencer, Soumelis, Vassili, Tangy, Frédéric, Tartour, Eric, Toubert, Antoine, Touvier, Mathilde, Ungeheuer, Marie‐Noëlle, Albert, Matthew L., Biomédecine computationelle des systèmes / Computational systems biomedicine, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Universität Zürich [Zürich] = University of Zurich (UZH), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Projet NECESSITY (PN), Hôpitaux Universitaires Paris Sud [AP-HP] (HUPS)-Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Immunologie Translationnelle - Translational Immunology lab, Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Ecole Polytechnique Fédérale de Lausanne (EPFL), Université de Lausanne = University of Lausanne (UNIL), Lausanne University Hospital, University of Bergen (UiB), Oklahoma Medical Research Foundation (OMRF), University of Oklahoma Health Sciences Center (OUHSC), Université de Strasbourg (UNISTRA), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Newcastle University [Newcastle], Newcastle Upon Tyne Hospitals NHS Foundation Trust, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Immunologie, Immunopathologie et Chimie Thérapeutique (I2CT), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Biogen Inc. [Cambridge, MA, USA], Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Supported by the Innovative Medicines Initiative 2 Joint Undertaking (JU) (grant 806975). The JU receives support from the European Union’s Horizon 2020 research and innovation program and the European Unionand the European Federation of Pharmaceutical Industries and Associations. This work was also supported by the National Institutes of Health (National Institute of Arthritis and Musculoskeletal Skin Disease grant R01-AR-065953). The Assessment of Systemic Signs and Evolution in Sjögren’s Syndrome(ASSESS) national multicenter prospective cohort was formed in 2006 with aFrench Ministry of Health grant (Programme Hospitalier de Recherche Clinique 2005 P060228). The ASSESS cohort is promoted by the French Society of Rheumatology and receives research grants from the French Society of Rheumatology. Dr. Gottenberg’s work was supported by Bristol Myers Squibbfor transcriptomic analysis of the ASSESS and Norwegian cohorts and by Geneviève Garnier (Association Française du Syndrome de Gougerot-Sjögrenet des syndromes secs). Drs. Trutschel’s and Schwikowski’s work was supported by Geneviève Garnier (Association Française du Syndrome de Gougerot-Sjögren et des syndromes secs)., Milieu Intérieur Consortium, ASSESS study investigators, and NECESSITY Consortium: Emmanuelle Dernis, Valerie Devauchelle-Pensec, Philippe Dieude, Jean-Jacques Dubost, Anne-Laure Fauchais, Vincent Goeb, Eric Hachulla, Pierre Yves Hatron, Claire Larroche, Véronique Le Guern, Jacques Morel, Aleth Perdriger, Carinne Salliot, Stephanie Rist, Alain Saraux, Jean Sibilia, Olivier Vittecoq, Gaétane Nocturne, Philippe Ravaud, Raphaèle Seror, Laurent Abel, Andres Alcover, Hugues Aschard, Kalla Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay, Odile Gelpi, Ivo GompertsBoneca, Milena Hasan, Serge Hercberg, Olivier Lantz, Claude Leclerc, Hugo Mouquet, Sandra Pellegrini, Stanislas Pol, Antonio Rausell, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Vassili Soumelis, Frédéric Tangy, Eric Tartour, Antoine Toubert, Mathilde Touvier, Marie-Noëlle Ungeheuer, Matthew L Albert, Darragh Duffy, Lluis Quintana-Murci., European Project: 806975,NECESSITY, Clauss, Isabelle, and NEw Clinical Endpoints in primary Sjögren’s Syndrome: an Interventional Trial based on stratifYing patients - NECESSITY - 0000-00-00 - 0000-00-00 - 806975 - VALID

Subjects
Proteomics, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Sjogren's Syndrome, Rheumatology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, HLA-DQ Antigens, Immunology, Humans, Interferon-alpha, Immunology and Allergy, Prospective Studies
Abstract

Objective: Primary Sjögren's syndrome (SS) is the second most frequent systemic autoimmune disease, affecting 0.1% of the general population. To characterize the molecular and clinical variabilities among patients with primary SS, we integrated transcriptomic, proteomic, cellular, and genetic data with clinical phenotypes in a cohort of 351 patients with primary SS. Methods: We analyzed blood transcriptomes and genotypes of 351 patients with primary SS who were participants in a multicenter prospective clinical cohort. We replicated the transcriptome analysis in 3 independent cohorts (n = 462 patients). We determined circulating interferon-α (IFNα) and IFNγ protein concentrations using digital single molecular arrays (Simoa). Results: Transcriptome analysis of the prospective cohort showed a strong IFN gene signature in more than half of the patients; this finding was replicated in the 3 independent cohorts. Because gene expression analysis did not discriminate between type I IFN and type II IFN, we used Simoa to demonstrate that the IFN transcriptomic signature was driven by circulating IFNα and not by IFNγ protein levels. IFNα protein levels, detectable in 75% of patients, were significantly associated with clinical and immunologic features of primary SS disease activity at enrollment and with increased frequency of systemic complications over the 5-year follow-up. Genetic analysis revealed a significant association between IFNα protein levels, a major histocompatibility (MHC) class II haplotype, and anti-SSA antibody. Additional cellular analysis revealed that an MHC class II HLA–DQ locus acts through up-regulation of HLA class II molecules on conventional dendritic cells. Conclusion: We identified the predominance of IFNα as a driver of primary SS variability, with IFNα demonstrating an association with HLA gene polymorphisms., Arthritis & Rheumatology, 74 (12), ISSN:2326-5191, ISSN:2326-5205

Published
2022
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12. Additional file 2 of Integrative genetic and immune cell analysis of plasma proteins in healthy donors identifies novel associations involving primary immune deficiency genes

Author

Caron, Barthelemy, Patin, Etienne, Rotival, Maxime, Charbit, Bruno, Albert, Matthew L., Quintana-Murci, Lluis, Duffy, Darragh, and Rausell, Antonio

Subjects
population characteristics, social sciences
Abstract

Additional file 2: Figure S1. Principal component analysis of age and sex effects. Figure S2. Manhattan plots and allelic expression of levels of cis-pQTLs. Figure S3. Manhattan plots and allelic expression of levels of trans-pQTLs. Figure S4. Impact of blood-cell fractions on associated protein-SNP pairs statistics.

Published
2022
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14. Early IFNβ secretion determines variable downstream IL-12p70 responses upon TLR4 activation

Author

Posseme, Celine, Llibre, Alba, Charbit, Bruno, Bondet, Vincent, Rouilly, Vincent, Saint-André, Violaine, Boussier, Jeremy, Bergstedt, Jacob, Smith, Nikaïa, Townsend, Liam, Sugrue, Jamie A., Ní Cheallaigh, Clíona, Conlon, Niall, Rotival, Maxime, Kobor, Michael S., Mottez, Estelle, Pol, Stanislas, Patin, Etienne, Albert, Matthew L., Quintana-Murci, Lluis, Duffy, Darragh, Abel, Laurent, Alcover, Andres, Aschard, Hugues, Bousso, Philippe, Bourke, Nollaig, Brodin, Petter, Bruhns, Pierre, Cerf-Bensussan, Nadine, Cumano, Ana, Demangel, Caroline, d’Enfert, Christophe, Deriano, Ludovic, Dillies, Marie-Agnès, Di Santo, James, Dromer, Françoise, Eberl, Gérard, Enninga, Jost, Fellay, Jacques, Gomperts-Boneca, Ivo, Hasan, Milena, Fontes, Magnus, Hedestam, Gunilla Karlsson, Hercberg, Serge, Ingersoll, Molly A., Kenny, Rose Anne, Lantz, Olivier, Ménager, Mickael, Michel, Frédérique, Mouquet, Hugo, O'Farrelly, Cliona, Patin, Etienne, Pellegrini, Sandra, Pol, Stanislas, Rausell, Antonio, Rieux-Laucat, Frédéric, Rogge, Lars, Sakuntabhai, Anavaj, Schwartz, Olivier, Schwikowski, Benno, Shorte, Spencer, Tangy, Frédéric, Toubert, Antoine, Touvier, Mathilde, Ungeheuer, Marie-Noëlle, Zimmer, Christophe, Albert, Matthew L., Duffy, Darragh, and Quintana-Murci, Lluis

Abstract

The interleukin-12 (IL-12) family comprises the only heterodimeric cytokines mediating diverse functional effects. We previously reported a striking bimodal IL-12p70 response to lipopolysaccharide (LPS) stimulation in healthy donors. Herein, we demonstrate that interferon β (IFNβ) is a major upstream determinant of IL-12p70 production, which is also associated with numbers and activation of circulating monocytes. Integrative modeling of proteomic, genetic, epigenomic, and cellular data confirms IFNβ as key for LPS-induced IL-12p70 and allowed us to compare the relative effects of each of these parameters on variable cytokine responses. Clinical relevance of our findings is supported by reduced IFNβ-IL-12p70 responses in patients hospitalized with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or chronically infected with hepatitis C (HCV). Importantly, these responses are resolved after viral clearance. Our systems immunology approach defines a better understanding of IL-12p70 and IFNβ in healthy and infected persons, providing insights into how common genetic and epigenetic variation may impact immune responses to bacterial infection.

Published
2022
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15. Enrichment of oral-derived bacteria in inflamed colorectal tumors and distinct associations of Fusobacteriumin the mesenchymal subtype

Author

Younginger, Brett S., Mayba, Oleg, Reeder, Jens, Nagarkar, Deepti R., Modrusan, Zora, Albert, Matthew L., and Byrd, Allyson L.

Abstract

While the association between colorectal cancer (CRC) features and Fusobacteriumhas been extensively studied, less is known of other intratumoral bacteria. Here, we leverage whole transcriptomes from 807 CRC samples to dually characterize tumor gene expression and 74 intratumoral bacteria. Seventeen of these species, including 4 Fusobacterium spp., are classified as orally derived and are enriched among right-sided, microsatellite instability-high (MSI-H), and BRAF-mutant tumors. Across consensus molecular subtypes (CMSs), integration of Fusobacterium animalis(Fa) presence and tumor expression reveals that Fahas the most significant associations in mesenchymal CMS4 tumors despite a lower prevalence than in immune CMS1. Within CMS4, the prevalence of Fais uniquely associated with collagen- and immune-related pathways. Additional Fapangenome analysis reveals that stress response genes and the adhesion FadA are commonly expressed intratumorally. Overall, this study identifies oral-derived bacteria as enriched in inflamed tumors, and the associations of bacteria and tumor expression are context and species specific.

Published
2023
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