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8. Convergent synthesis of glycoalkaloids solasonine and its saponin derivative.

Author

Yang, Yue, Li, Tong, Hao, Huiran, Sheng, Ju-Zheng, Li, Tianlu, and Peng, Peng

Subjects
GLYCOALKALOIDS, CYANIDES, DISACCHARIDES, MOIETIES (Chemistry), CATALYSIS
Abstract

We present a practical and convergent synthesis of glycoalkaloids solasonine 1 and its saponin derivative 2, incorporating a {3-O-α- L -rhamnopyranosyl-(1→2)-O-[β- D -glucopyranosyl-(1→3)]-β- D -galactopyranoside} moiety. The key features of this strategy include the following: (1) AuCl3–tBuCN cooperative catalysis enabling 1,2-trans stereoselective glycosidation of 2-branched trisaccharide trichloroacetimidate donors with steroidal aglycons, in the absence of neighboring group participation; (2) "cyanide effect" mediated regioselective benzoylation of the 4- and 6-hydroxyl groups of galactopyranosyl disaccharide; and (3) an effective approach to prevent orthoester byproduct formation. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Targeting aberrant DNA methylation in mesenchymal stromal cells as a treatment for myeloma bone disease

Author

Garcia-Gomez, Antonio, Li, Tianlu, de la Calle-Fabregat, Carlos, Rodríguez-Ubreva, Javier, Ciudad, Laura, Català-Moll, Francesc, Godoy-Tena, Gerard, Martín-Sánchez, Montserrat, San-Segundo, Laura, Muntión, Sandra, Morales, Xabier, Ortiz-de-Solórzano, Carlos, Oyarzabal, Julen, San José-Enériz, Edurne, Esteller, Manel, Agirre, Xabier, Prosper, Felipe, Garayoa, Mercedes, and Ballestar, Esteban

Published
2021
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19. Contributors

Author

Ballestar, Esteban, primary, Bhat, Jaydeep, additional, Bhat, Sajad Ahmad, additional, Chen, Ziyi, additional, Chiplunkar, Shubhada, additional, deSouza, Anjali, additional, DeVries, Avery, additional, Ferreira, Humberto J., additional, Galande, Sanjeev, additional, Giri, Ashok, additional, Gomes, Anita Q., additional, Hakobyan, Mariam, additional, Hartmann, Mark, additional, Hinkley, Emily, additional, Kabelitz, Dieter, additional, Kotkar, Hemlata, additional, Langstein, Jens, additional, Li, Jasmine, additional, Li, Tianlu, additional, Li, Wenhui, additional, Lipka, Daniel B., additional, Machnicka, Magdalena A., additional, Madhok, Ayush, additional, Philip, Chinna Susan, additional, Piro, Rosario Michael, additional, Placek, Katarzyna, additional, Qin, F. Xiao-Feng, additional, Rodríguez-Ubreva, Javier, additional, Russ, Brendan E., additional, Saglam, Adem, additional, Schmolka, Nina, additional, Schönung, Maximilian, additional, Schulte-Schrepping, Jonas, additional, Schultze, Joachim L., additional, Silva-Santos, Bruno, additional, Stäble, Sina, additional, Sureshbabu, Shalini Kashipathi, additional, Touzart, Aurore, additional, Turner, Stephen J., additional, Vercelli, Donata, additional, Wierzbinska, Justyna A., additional, Wilczynski, Bartek, additional, Wu, Aiping, additional, and Zhang, Lianjun, additional

Published
2020
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23. Hepatitis C co-infection characteristics and correlates in newly reported HIV/AIDS patients in Southwest China, 2018–2022

Author

Zhang, Yulian, Jike, Chunnong, Yu, Gang, Wang, Ju, Wang, Zhonghong, Ma, Lazuo, Li, Tianlu, Li, Yuan, and Pei, Rong

Abstract

Aims: The aims of the project were: (1) to map the current HIV–HCV co-infection in Liangshan Prefecture, Sichuan Province, China, (2) to explore the risk factors of HIV–HCV co-infection in Liangshan Prefecture, and (3) to propose strategies for prevention and control of HIV–HCV co-infection in Liangshan Prefecture. Subject and methods: This study assessed the HIV–HCV co-infection rate, characteristics, and correlative factors of HIV–HCV co-infection individuals reported between 2018 and 2022 in Liangshan. This made use of path analysis, multiple logistic regression analysis, and chi-square tests. Results: The findings revealed a 6.75% HIV–HCV co-infection rate, and the incidence was stable from 2018 to 2022. The outcomes of multiple logistic regression showed the correlative factors, including male (OR = 2.640, 95% CI: 2.300–3.031), 25–44 years (OR = 4.184, 95% CI: 2.135–8.196), 45–64 years (OR = 3.411, 95% CI: 1.733–0.937), Anning River Valley (OR = 2.583, 95% CI: 1.833–3.639) and east of it (OR = 2.543, 95% CI: 1.749–3.699), and injecting drug use (OR = 2.116, 95% CI: 1.879–2.383). The pathway analysis revealed that co-infection was directly influenced by gender (−0.112), ethnicity (−0.079), marital status (0.077), and route of infection (−0.095). Conclusion: Concentrate on the high-risk group based on the co-infection associated factors found in the study's findings. Take the necessary steps to enhance patient quality of life and survival, as well as the efficacy of preventive treatment and therapy.

Published
2024
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30. Methylome and transcriptome profiling of giant cell arteritis monocytes reveals novel pathways involved in disease pathogenesis and molecular response to glucocorticoids

Author

Estupiñán-Moreno, Elkyn, primary, Ortiz-Fernández, Lourdes, additional, Li, Tianlu, additional, Hernández-Rodríguez, Jose, additional, Ciudad, Laura, additional, Andrés-León, Eduardo, additional, Terron-Camero, Laura Carmen, additional, Prieto-González, Sergio, additional, Espígol-Frigolé, Georgina, additional, Cid, Maria Cinta, additional, Márquez, Ana, additional, Ballestar, Esteban, additional, and Martín, Javier, additional

Published
2022
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31. Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis

Author

Julià, Antonio, primary, Gómez, Antonio, additional, López-Lasanta, María, additional, Blanco, Francisco, additional, Erra, Alba, additional, Fernández-Nebro, Antonio, additional, Mas, Antonio Juan, additional, Pérez-García, Carolina, additional, Vivar, Ma Luz García, additional, Sánchez-Fernández, Simón, additional, Alperi-López, Mercedes, additional, Sanmartí, Raimon, additional, Ortiz, Ana María, additional, Fernandez-Cid, Carlos Marras, additional, Díaz-Torné, César, additional, Moreno, Estefania, additional, Li, Tianlu, additional, Martínez-Mateu, Sergio H., additional, Absher, Devin M., additional, Myers, Richard M., additional, Molina, Jesús Tornero, additional, and Marsal, Sara, additional

Published
2022
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40. Vitamin D receptor, STAT3, and TET2 cooperate to establish tolerogenesis

Author

Català-Moll, Francesc, primary, Ferreté-Bonastre, Anna G., additional, Godoy-Tena, Gerard, additional, Morante-Palacios, Octavio, additional, Ciudad, Laura, additional, Barberà, Laura, additional, Fondelli, Federico, additional, Martínez-Cáceres, Eva M., additional, Rodríguez-Ubreva, Javier, additional, Li, Tianlu, additional, and Ballestar, Esteban, additional

Published
2022
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41. Tribocorrosion behavior of Ca–P MAO coatings on Ti6Al4V alloy at various applied voltages

Author

Fei Chen, You Zhang, Li Tianlu, Jiang Xinyun, Zuo You, and Minbao Wu

Subjects
Anatase, Materials science, Mechanical Engineering, Tribocorrosion, Simulated body fluid, 02 engineering and technology, Tribology, engineering.material, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Dielectric spectroscopy, Corrosion, 020303 mechanical engineering & transports, 0203 mechanical engineering, Coating, Mechanics of Materials, Surface roughness, engineering, General Materials Science, Composite material, 0210 nano-technology
Abstract

In this study, coatings containing Ca and P elements on Ti6Al4V alloy were fabricated by micro-arc oxidation at different applied voltages. Subsequently, evaluation of the phase structure, morphology, element composition, corrosion mechanism, and tribocorrosion behavior of these coatings was performed. The results showed that the coatings consisted of rutile TiO2 and anatase TiO2. The ratio of rutile/anatase, surface roughness, and hardness increase with the increase of applied voltage. Electrochemical impedance spectroscopy results indicated the corrosion resistance of coatings in simulated body fluid of 400 V > 380 V > 420 V. The open circuit potential of sample 400 V declined during the tribocorrosion test. Sample 420 V possessed the highest wear volume after the tribocorrosion process. The tribocorrosion mechanism of samples 380 and 420 V was mainly confirmed as the wear effect, and the decline of corrosion resistance due to the micro-cracks formed during the abrasive wear of the coating accounts for the tribocorrosion mechanism of sample 400 V.

Published
2019

42. A new molecular classification to drive precision treatment strategies in primary Sjögren’s syndrome

Author

Soret, Perrine, Le Dantec, Christelle, Desvaux, Emiko, Foulquier, Nathan, Chassagnol, Bastien, Hubert, Sandra, Christophe, Jamin, Barturen, Guillermo, Desachy, Guillaume, Devauchelle-Pensec, Valérie, Boudjeniba, Cheïma, Cornec, Divi, Saraux, Alain, Jousse-Joulin, Sandrine, Barbarroja, Nuria, Rodríguez-Pintó, Ignasi, de Langhe, Ellen, Beretta, Lorenzo, Chizzolini, Carlo, Kovács, László, Witte, Torsten, Bettacchioli, Eléonore, Buttgereit, Anne, Makowska, Zuzanna, Lesche, Ralf, Borghi, Maria Orietta, Martin, Javier, Courtade-Gaiani, Sophie, Xuereb, Laura, Guedj, Mickaël, Moingeon, Philippe, Alarcón-Riquelme, Marta, Laigle, Laurence, Pers, Jacques-Olivier, Vigone, Barbara, Lauwerys, Bernard, Maudoux, Anne-Lise, Vasconcelos, Carlos, Tavares, Ana, Faria, Raquel, Brandão, Mariana, Campar, Ana, Marinho, António, Farinha, Fátima, Almeida, Isabel, Gonzalez-Gay Mantecón, Miguel Angel, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Cervera, Ricard, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega-Castro, Rafaela, Aguirre-Zamorano, Ma Angeles, Escudero-Contreras, Alejandro, Castro-Villegas, Ma Carmen, Jiménez Gómez, Yolanda, Ortego, Norberto, Fernández Roldán, María Concepción, Raya, Enrique, Jiménez Moleón, Inmaculada, de Ramon, Enrique, Díaz Quintero, Isabel, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, Zuber, Aleksandra, Wynar, Donatienne, Balog, Attila, Deák, Magdolna, Bocskai, Márta, Dulic, Sonja, Kádár, Gabriella, Hiepe, Falk, Thiel, Silvia, Rodriguez Maresca, Manuel, López-Berrio, Antonio, Aguilar-Quesada, Rocío, Navarro-Linares, Héctor, Ioannou, Yiannis, Chamberlain, Chris, Marovac, Jacqueline, Alarcón Riquelme, Marta, Gomes Anjos, Tania, Marañón, Concepción, Le Lann, Lucas, Simon, Quentin, Rouvière, Bénédicte, Varela, Nieves, Muchmore, Brian, Dufour, Aleksandra, Alvarez, Montserrat, Cremer, Jonathan, Lopez-Pedrera, Chary, Gerl, Velia, Khodadadi, Laleh, Cheng, Qingyu, de Groof, Aurélie, Ducreux, Julie, Trombetta, Elena, Li, Tianlu, Alvarez-Errico, Damiana, Kniesch, Katja, Azevedo, Nancy, Neves, Esmeralda, Rao, Sambasiva, Jouve, Pierre-Emmanuel, Institut de Recherches Internationales Servier [Suresnes] (IRIS), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre for Genomics and Oncological Reearch (GENYO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba = University of Córdoba [Córdoba]-Hospital Universitario Reina Sofía, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Maggiore Hospital, IRCCS Foundation, Milano, Department of Pathology and Immunology [Geneva, Switzerland], Université de Genève = University of Geneva (UNIGE), University of Szeged [Szeged], Clinic for Immunology and Rhematology, Hannover Medical School, Hanover, Germany, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Pharmaceuticals Division Bayer Pharma Aktiengesellschaft, Università degli Studi di Milano = University of Milan (UNIMI), Instituto de Parasitología y Biomedicina 'López-Neyra' (IPBLN), Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Granada = University of Granada (UGR), and Michel, Geneviève

Subjects
MESH: Databases, Protein, MESH: Inflammation, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Flow Cytometry, MESH: Cross-Sectional Studies, MESH: DNA Methylation, MESH: Computer Simulation, cell cycle, chronic lymphocytic leukemia, liquid chromatography-tandem mass spectrometry, splicing, MESH: Autoantibodies, MESH: Interferons, MESH: RNA-Seq, MESH: Cohort Studies, MESH: Databases, Genetic, MESH: Cytokines, MESH: Humans, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, MESH: Transcriptome, MESH: Adult, MESH: Chemokines, MESH: Male, MESH: Proteome, MESH: Sjogren's Syndrome, MESH: Genome-Wide Association Study, MESH: Biomarkers, MESH: Multigene Family, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Female, MESH: Computational Biology
Abstract

International audience; Abstract There is currently no approved treatment for primary Sjögren’s syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjögren’s syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning classifiers to sort future patients into subgroups, allowing the re-evaluation of response to treatments in clinical trials.

Published
2021

44. Coordinated glucocorticoid receptor and MAFB action induces tolerogenesis and epigenome remodeling in dendritic cells

Author

Morante-Palacios, Octavio, primary, Ciudad, Laura, additional, Micheroli, Raphael, additional, de la Calle-Fabregat, Carlos, additional, Li, Tianlu, additional, Barbisan, Gisela, additional, Houtman, Miranda, additional, Edalat, Sam G, additional, Frank-Bertoncelj, Mojca, additional, Ospelt, Caroline, additional, and Ballestar, Esteban, additional

Published
2021
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48. Effect of graphene oxide additive on tribocorrosion behavior of MAO coatings prepared on Ti6Al4V alloy

Author

Chen Xiaoyi, You Zhang, Zhao Zicong, Fei Chen, Zuo You, Peihang Yu, and Li Tianlu

Subjects
Materials science, Tribocorrosion, Oxide, General Physics and Astronomy, chemistry.chemical_element, 02 engineering and technology, engineering.material, 010402 general chemistry, 01 natural sciences, law.invention, Corrosion, chemistry.chemical_compound, Coating, law, Composite material, Polarization (electrochemistry), Graphene, Surfaces and Interfaces, General Chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 0104 chemical sciences, Surfaces, Coatings and Films, Dielectric spectroscopy, chemistry, engineering, 0210 nano-technology, Titanium
Abstract

Titanium and its alloys possess the superiority on corrosion resistance and the shortage on wear resistance. Tribocorrosion, a new study orientation concerning both corrosion and wear resistances and fascinating researchers in recent years, has to be considered on the titanium, its alloys and their surface treated materials. In this study, graphene oxide (GO) particles inserted coatings were prepared by micro-arc oxidation (MAO) treatment with various GO concentrations. The composition, morphology and topography were measured to analyze the structure and properties of coatings. Electrochemical impedance spectroscopy (EIS) and polarization measurements were utilized to assess the corrosion resistance of samples. Tribocorrosion behavior was evaluated by the open circuit potential (OCP) and coefficient of friction (COF) evolutions in advance to, during and after reciprocating sliding. The results showed that in GO concentration of 5 mL/L and 10 mL/L, the GO particles were inserted into the MAO coatings and the MAO coating by adding 10 mL/L GO particles possessed best tribocorrosion resistance.

Published
2019

49. Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

Author

Teruel, María, Barturen, Guillermo, Martínez Bueno, Manuel, Castellini Pérez, Olivia, Barroso Gil, Miguel, Povedano, Elena, Kerick, Martin, Català Moll, Francesc, Makowska, Zuzanna, Buttgereit, Anne, Beretta, Lorenzo, Chizzolini, Carlo, Zuber, Aleksandra, Wynar, Donatienne, Kovács, Laszló, Balog, Attila, Deák, Magdolna, Bocskai, Márta, Dulic, Sonja, Kádár, Gabriella, Hiepe, Falk, Gerl, Velia, Thiel, Silvia, Rodriguez Maresca, Manuel, López Berrio, Antonio, Aguilar Quesada, Rocío, Navarro Linares, Héctor, Alvarez, Montserrat, Álvarez Errico, Damiana, Azevedo, Nancy, Barbarroja, Nuria, Cheng, Qingyu, Cremer, Jonathan, Groof, Aurélie de, Langhe, Ellen de, Ducreux, Julie, Dufour, Aleksandra, Hernández Fuentes, María, Khodadadi, Laleh, Kniesch, Katja, Li, Tianlu, López Pedrera, Chary, Marañón, Concepción, Muchmore, Brian, Neves, Esmeralda, Rouvière, Bénédicte, Simon, Quentin, Trombetta, Elena, Varela, Nieves, Witte, Torsten, Pers, Jacques-olivier, Ballestar, Esteban, Martin, Javier, Carnero Montoro, Elena, Alarcón Riquelme, Marta, Precisesads Clinical Consortium, Precisesads Flow Cytometry Study Group, Vigone, Barbara, Pers, Jacques Olivier, Saraux, Alain, Devauchelle-Pensec, Valérie, Cornec, Divi, Jousse-Joulin, Sandrine, Lauwerys, Bernard, Maudoux, Anne-lise, Vasconcelos, Carlos, Tavares, Ana, Faria, Raquel, Brandão, Mariana, Campar, Ana, Marinho, António, Farinha, Fátima, Almeida, Isabel, Gonzalez-Gay Mantecón, Miguel Ángel, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Cervera, Ricard, Rodríguez Pintó, Ignasi, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega Castro, Rafaela, Aguirre Zamorano, Mª Angeles, Escudero Contreras, Alejandro, Castro Villegas, Mª Carmen, Ortego, Norberto, Fernández Roldán, María Concepción, Raya, Enrique, Jiménez Moleón, Inmaculada, Ramon, Enrique de, Díaz Quintero, Isabel, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, PRECISESADS Clinical Consortium, PRECISESADS Flow Cytometry Study Group, [Teruel,M, Barturen,G, Martínez-Bueno,M, Castellini-Pérez,O, Barroso-Gil,M, Povedano,E, Marañón,C, Carnero-Montoro,E, Alarcón-Riquelme,ME] GENYO, Center for Genomics and Oncological Research Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain. [Kerick,M, Martin,J] IPBLN-CSIC, Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científcas, Granada, Spain. [Català-Moll,F, Ballestar,E] Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC), Badalona, Barcelona, Spain. [Català-Moll,F, Ballestar,E] IDIBELL, Bellvitge Biomedical Research Institute L’Hospitalet de Llobregat, Barcelona, Spain. [Makowska,Z, Buttgereit,A] Pharmaceuticals Division, Bayer Pharma Aktiengesellschaft, Berlin, Germany. [Pers,JO] Université de Brest, INSERM, Labex IGO, CHU de Brest, Brest, France.[Alarcón-Riquelme,ME] Institute for Environmental Medicine, Karolinska Institutet, Solna, Sweden., and Funding for the preparation of this manuscript has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement nº 115,565, resources composed of the financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and the EFPIA companies’ in kind contribution. MT is supported by a Spanish grant from Health Department, Junta de Andalucía (PI/0017/2016) and through the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806975. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. EC-M was funded by the Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness (FJCI_2014_20652). We thank Ralf Lesche for the production of RNASeq data and Marc Torres Ciuró for design support.

Subjects
Epigenomics, Male, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation [Medical Subject Headings], Autoimmune diseases, Gene Expression, Quantitative trait, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Interferons [Medical Subject Headings], 0302 clinical medicine, Rheumatic diseases, HLA Antigens, Genetics, Regulation of gene expression, 0303 health sciences, education.field_of_study, Multidisciplinary, Malalties autoimmunitàries, Molecular medicine, Epigenetic, Autoanticuerpos, Genomics, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics::Epigenomics [Medical Subject Headings], 3. Good health, Sjogren's Syndrome, DNA methylation, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::DNA Methylation [Medical Subject Headings], Medicine, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA Antigens [Medical Subject Headings], Epigenetics, Female, Phenomena and Processes::Genetic Phenomena::Genetic Variation [Medical Subject Headings], Extracellular matrix organization, Science, Population, Check Tags::Male [Medical Subject Headings], Human leukocyte antigen, Biology, Variación genética, Article, 03 medical and health sciences, Rheumatology, Enfermedades autoinmunes, Diseases::Immune System Diseases::Autoimmune Diseases [Medical Subject Headings], Immunogenetics, Diseases::Immune System Diseases::Autoimmune Diseases::Arthritis, Rheumatoid::Sjogren's Syndrome [Medical Subject Headings], Humans, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies [Medical Subject Headings], education, Gene, 030304 developmental biology, Autoantibodies, 030203 arthritis & rheumatology, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic [Medical Subject Headings], Genetic Variation, DNA Methylation, Epigenètica, Check Tags::Female [Medical Subject Headings], Gene Expression Regulation, Epigenómica, Síndrome de Sjögren, Interferons, Expresión génica
Abstract

Funding for the preparation of this manuscript has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no 115,565, resources composed of the financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and the EFPIA companies' in kind contribution. MT is supported by a Spanish grant from Health Department, Junta de Andalucia (PI/0017/2016) and through the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806975. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. EC-M was funded by the Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness (FJCI_2014_20652). We thank Ralf Lesche for the production of RNASeq data and Marc Torres Ciuro for design support., Primary Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population., Innovative Medicines Initiative Joint Undertaking from the European Union's Seventh Framework Program (FP7/2007-2013) 115,565, EFPIA companies, Junta de Andalucia PI/0017/2016, Innovative Medicines Initiative 2 Joint Undertaking 806975 European Union's Horizon 2020 research and innovation programme, EFPIA, Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness FJCI_2014_20652

Published
2021

50. Epigenomics and transcriptomics of systemic sclerosis CD4+ T cells reveal long-range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci

Author

Li, Tianlu, Ortiz-Fernández, L., Andrés-León, E., Ciudad, Laura, Javierre, BM, López-Isac, E., Guillén-Del-Castillo, A., Simeón-Aznar, C.P., Ballestar, Esteban, Martin, J., Universitat Autònoma de Barcelona, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Generalitat de Catalunya, Josep Carreras Leukemia Foundation, Instituto de Salud Carlos III, and European Commission

Subjects
CD4-Positive T-Lymphocytes, Epigenomics, lcsh:QH426-470, T cell, lcsh:Medicine, Biology, Epigenesis, Genetic, Transcriptome, Epigenome, Immune system, Hi-C, Genetics, medicine, Humans, Genetic Predisposition to Disease, Epigenetics, Genetic susceptibility variants, Molecular Biology, Genetics (clinical), Genetic Association Studies, Scleroderma, Systemic, DNA methylation, Gene Expression Profiling, Research, lcsh:R, NF-kappa B, Computational Biology, CTCF, Long-distance regulation, lcsh:Genetics, medicine.anatomical_structure, CpG site, Genetic Loci, Molecular Medicine, Systemic sclerosis, Signal Transduction
Abstract

© The Author(s). 2020., [Background]: Systemic sclerosis (SSc) is a genetically complex autoimmune disease mediated by the interplay between genetic and epigenetic factors in a multitude of immune cells, with CD4+ T lymphocytes as one of the principle drivers of pathogenesis., [Methods]: DNA samples exacted from CD4+ T cells of 48 SSc patients and 16 healthy controls were hybridized on MethylationEPIC BeadChip array. In parallel, gene expression was interrogated by hybridizing total RNA on Clariom™ S array. Downstream bioinformatics analyses were performed to identify correlating differentially methylated CpG positions (DMPs) and differentially expressed genes (DEGs), which were then confirmed utilizing previously published promoter capture Hi-C (PCHi-C) data., [Results]: We identified 9112 and 3929 DMPs and DEGs, respectively. These DMPs and DEGs are enriched in functional categories related to inflammation and T cell biology. Furthermore, correlation analysis identified 17,500 possible DMP-DEG interaction pairs within a window of 5 Mb, and utilizing PCHi-C data, we observed that 212 CD4+ T cell-specific pairs of DMP-DEG also formed part of three-dimensional promoter-enhancer networks, potentially involving CTCF. Finally, combining PCHi-C data with SSc GWAS data, we identified four important SSc-associated susceptibility loci, TNIP1 (rs3792783), GSDMB (rs9303277), IL12RB1 (rs2305743), and CSK (rs1378942), that could potentially interact with DMP-DEG pairs cg17239269-ANXA6, cg19458020-CCR7, cg10808810-JUND, and cg11062629-ULK3, respectively., [Conclusion]: Our study unveils a potential link between genetic, epigenetic, and transcriptional deregulation in CD4+ T cells of SSc patients, providing a novel integrated view of molecular components driving SSc pathogenesis., We thank CERCA Programme/Generalitat de Catalunya and the Josep Carreras Foundation for institutional support. E.B. was funded by the Ministry of Science and Innovation (MICINN; grant number SAF2017-88086-R). J.M. was funded by the Ministry of Science and Innovation (MICINN; grant number RT2018-101332-B-I00). J.M. and E.B. are supported by RETICS network grant from ISCIII (RIER, RD16/0012/0013), FEDER “Una manera de hacer Europa.”

Published
2021

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