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1. Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation

Author

Mijnheer, Gerdien, Lutter, Lisanne, Mokry, Michal, van der Wal, Marlot, Scholman, Rianne, Fleskens, Veerle, Pandit, Aridaman, Tao, Weiyang, Wekking, Mark, Vervoort, Stephin, Roberts, Ceri, Petrelli, Alessandra, Peeters, Janneke G. C., Knijff, Marthe, de Roock, Sytze, Vastert, Sebastiaan, Taams, Leonie S., van Loosdregt, Jorg, and van Wijk, Femke

Published
2021
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3. Epigenetic changes in inflammatory arthritis monocytes contribute to disease and can be targeted by JAK inhibition

Author

CMM Groep Coffer, CDL Cluster Onderzoek en Onderwijs, CTI Van Loosdregt, CMM Sectie Stem Cells, Onderzoek, Cancer, Infection & Immunity, Regenerative Medicine and Stem Cells, CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Child Health, Circulatory Health, Immuno/reuma onderzoek 1 (Vastert), Immunologie/Reumatologie, CTI Van Wijk, CTI Research, Immuno/reuma onderzoek 3 (Loosdregt), Peeters, Janneke G C, Boltjes, Arjan, Scholman, Rianne C, Vervoort, Stephin J, Coffer, Paul J, Mokry, Michal, Vastert, Sebastiaan J, van Wijk, Femke, van Loosdregt, Jorg, CMM Groep Coffer, CDL Cluster Onderzoek en Onderwijs, CTI Van Loosdregt, CMM Sectie Stem Cells, Onderzoek, Cancer, Infection & Immunity, Regenerative Medicine and Stem Cells, CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Child Health, Circulatory Health, Immuno/reuma onderzoek 1 (Vastert), Immunologie/Reumatologie, CTI Van Wijk, CTI Research, Immuno/reuma onderzoek 3 (Loosdregt), Peeters, Janneke G C, Boltjes, Arjan, Scholman, Rianne C, Vervoort, Stephin J, Coffer, Paul J, Mokry, Michal, Vastert, Sebastiaan J, van Wijk, Femke, and van Loosdregt, Jorg

Published
2023

4. Epigenetic changes in inflammatory arthritis monocytes contribute to disease and can be targeted by JAK inhibition.

Author

Peeters, Janneke G C, Boltjes, Arjan, Scholman, Rianne C, Vervoort, Stephin J, Coffer, Paul J, Mokry, Michal, Vastert, Sebastiaan J, Wijk, Femke van, and Loosdregt, Jorg van

Subjects
*CHROMOSOMES, *SEQUENCE analysis, *RNA, *PRECIPITIN tests, *JANUS kinases, *RHEUMATOID arthritis, *RESEARCH funding, *NEUROTRANSMITTER uptake inhibitors, *TRANSCRIPTION factors, *EPIGENOMICS, *MONOCYTES, *SYNOVIAL fluid, *PHENOTYPES
Abstract

Objectives How the local inflammatory environment regulates epigenetic changes in the context of inflammatory arthritis remains unclear. Here we assessed the transcriptional and active enhancer profile of monocytes derived from the inflamed joints of JIA patients, a model well-suited for studying inflammatory arthritis. Methods RNA sequencing and H3K27me3 chromatin immunoprecipitation sequencing (ChIP-seq) were used to analyse the transcriptional and epigenetic profile, respectively, of JIA synovial fluid-derived monocytes. Results Synovial-derived monocytes display an activated phenotype, which is regulated on the epigenetic level. IFN signalling-associated genes are increased and epigenetically altered in synovial monocytes, indicating a driving role for IFN in establishing the local inflammatory phenotype. Treatment of synovial monocytes with the Janus-associated kinase (JAK) inhibitor ruxolitinib, which inhibits IFN signalling, transformed the activated enhancer landscape and reduced disease-associated gene expression, thereby inhibiting the inflammatory phenotype. Conclusion This study provides novel insights into epigenetic regulation of inflammatory arthritis patient-derived monocytes and highlights the therapeutic potential of epigenetic modulation for the treatment of inflammatory rheumatic diseases. [ABSTRACT FROM AUTHOR]

Published
2023
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7. Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation

Author

Infection & Immunity, MMB Research line 1, CTI Van Wijk, Onderzoek Precision medicine, Child Health, Circulatory Health, CTI Van Loosdregt, CTI Pandit, Lab Reumatologie/Klinische Immunologie, CTI Research, CMM Groep Coffer, Immuno/reuma onderzoek 1 (Vastert), Immuno/reuma onderzoek 5 (Vastert2), Immuno/reuma onderzoek 3 (Loosdregt), Mijnheer, Gerdien, Lutter, Lisanne, Mokry, Michal, van der Wal, Marlot, Scholman, Rianne, Fleskens, Veerle, Pandit, Aridaman, Tao, Weiyang, Wekking, Mark, Vervoort, Stephin, Roberts, Ceri, Petrelli, Alessandra, Peeters, Janneke G C, Knijff, Marthe, de Roock, Sytze, Vastert, Sebastiaan, Taams, Leonie S, van Loosdregt, Jorg, van Wijk, Femke, Infection & Immunity, MMB Research line 1, CTI Van Wijk, Onderzoek Precision medicine, Child Health, Circulatory Health, CTI Van Loosdregt, CTI Pandit, Lab Reumatologie/Klinische Immunologie, CTI Research, CMM Groep Coffer, Immuno/reuma onderzoek 1 (Vastert), Immuno/reuma onderzoek 5 (Vastert2), Immuno/reuma onderzoek 3 (Loosdregt), Mijnheer, Gerdien, Lutter, Lisanne, Mokry, Michal, van der Wal, Marlot, Scholman, Rianne, Fleskens, Veerle, Pandit, Aridaman, Tao, Weiyang, Wekking, Mark, Vervoort, Stephin, Roberts, Ceri, Petrelli, Alessandra, Peeters, Janneke G C, Knijff, Marthe, de Roock, Sytze, Vastert, Sebastiaan, Taams, Leonie S, van Loosdregt, Jorg, and van Wijk, Femke

Published
2021

9. SOX4 can redirect TGF-β-mediated SMAD3-transcriptional output in a context-dependent manner to promote tumorigenesis

Author

Vervoort, Stephin J, primary, Lourenço, Ana Rita, additional, Tufegdzic Vidakovic, Ana, additional, Mocholi, Enric, additional, Sandoval, José L, additional, Rueda, Oscar M, additional, Frederiks, Cynthia, additional, Pals, Cornelieke, additional, Peeters, Janneke G C, additional, Caldas, Carlos, additional, Bruna, Alejandra, additional, and Coffer, Paul J, additional

Published
2018
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11. Increased autophagy contributes to the inflammatory phenotype of juvenile idiopathic arthritis synovial fluid T cells

Author

Immunologie onderzoek 2, Infection & Immunity, CMM Groep Coffer, JC onderzoeksprogramma Methodologie, Medical Humanities Onderzoek Team 2, Immuno/reuma onderzoek 1 (Vastert), CTI Van Loosdregt, Child Health, CMM, Peeters, Janneke G. C., de Graeff, Nienke, Lotz, Martin, Albani, Salvatore, de Roock, Sytze, van Loosdregt, Jorg, Immunologie onderzoek 2, Infection & Immunity, CMM Groep Coffer, JC onderzoeksprogramma Methodologie, Medical Humanities Onderzoek Team 2, Immuno/reuma onderzoek 1 (Vastert), CTI Van Loosdregt, Child Health, CMM, Peeters, Janneke G. C., de Graeff, Nienke, Lotz, Martin, Albani, Salvatore, de Roock, Sytze, and van Loosdregt, Jorg

Published
2017

12. Enhancers in autoimmune arthritis: Implications and therapeutic potential

Author

Infection & Immunity, CMM Groep Coffer, Child Health, Reumatologie patientenzorg, Immuno/reuma onderzoek 1 (Vastert), CTI Van Wijk, Immunologie onderzoek 2, Peeters, Janneke G. C., Vastert, Sebastiaan J, van Wijk, Femke, van Loosdregt, Jorg, Infection & Immunity, CMM Groep Coffer, Child Health, Reumatologie patientenzorg, Immuno/reuma onderzoek 1 (Vastert), CTI Van Wijk, Immunologie onderzoek 2, Peeters, Janneke G. C., Vastert, Sebastiaan J, van Wijk, Femke, and van Loosdregt, Jorg

Published
2017

13. Autoimmune disease-associated gene expression is reduced by BET-inhibition

Author

Peeters, Janneke G C, Vervoort, Stephin J, Mijnheer, Gerdien, de Roock, Sytze, Vastert, Sebastiaan J, Nieuwenhuis, Edward E S, van Wijk, Femke, Prakken, Berent J, Mokry, Michal, van Loosdregt, Jorg, Peeters, Janneke G C, Vervoort, Stephin J, Mijnheer, Gerdien, de Roock, Sytze, Vastert, Sebastiaan J, Nieuwenhuis, Edward E S, van Wijk, Femke, Prakken, Berent J, Mokry, Michal, and van Loosdregt, Jorg

Published
2016

14. Autoimmune disease-associated gene expression is reduced by BET-inhibition

Author

CMM Groep Coffer, CTI Van Wijk, Infection & Immunity, CTI Van Loosdregt, Child Health, Reumatologie patientenzorg, Zorg en O&O, Regenerative Medicine and Stem Cells, Immuno/reuma onderzoek 1 (Vastert), Circulatory Health, CTI Vastert, Reumatologie onderzoek 2, Divisieleiding O&O, MDL onderzoek 3, Immunologie onderzoek 2, Peeters, Janneke G C, Vervoort, Stephin J, Mijnheer, Gerdien, de Roock, Sytze, Vastert, Sebastiaan J, Nieuwenhuis, Edward E S, van Wijk, Femke, Prakken, Berent J, Mokry, Michal, van Loosdregt, Jorg, CMM Groep Coffer, CTI Van Wijk, Infection & Immunity, CTI Van Loosdregt, Child Health, Reumatologie patientenzorg, Zorg en O&O, Regenerative Medicine and Stem Cells, Immuno/reuma onderzoek 1 (Vastert), Circulatory Health, CTI Vastert, Reumatologie onderzoek 2, Divisieleiding O&O, MDL onderzoek 3, Immunologie onderzoek 2, Peeters, Janneke G C, Vervoort, Stephin J, Mijnheer, Gerdien, de Roock, Sytze, Vastert, Sebastiaan J, Nieuwenhuis, Edward E S, van Wijk, Femke, Prakken, Berent J, Mokry, Michal, and van Loosdregt, Jorg

Published
2016

15. Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression

Author

Peeters, Janneke G C, Vervoort, Stephin J, Tan, Sander C, Mijnheer, Gerdien, de Roock, Sytze, Vastert, Sebastiaan J., Nieuwenhuis, Edward E S, van Wijk, Femke, Prakken, Berent J, Creyghton, Menno P, Coffer, Paul J, Mokry, Michal, van Loosdregt, Jorg, Peeters, Janneke G C, Vervoort, Stephin J, Tan, Sander C, Mijnheer, Gerdien, de Roock, Sytze, Vastert, Sebastiaan J., Nieuwenhuis, Edward E S, van Wijk, Femke, Prakken, Berent J, Creyghton, Menno P, Coffer, Paul J, Mokry, Michal, and van Loosdregt, Jorg

Published
2015

16. Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression

Author

CMM Groep Coffer, CTI Van Wijk, Infection & Immunity, CTI Van Loosdregt, Child Health, Immuno/reuma onderzoek 1 (Vastert), Reumatologie patientenzorg, Zorg en O&O, Regenerative Medicine and Stem Cells, Circulatory Health, CTI Vastert, Reumatologie onderzoek 2, Hubrecht Institute with UMC, Immunologie onderzoek 2, Cancer, MDL onderzoek 3, Peeters, Janneke G C, Vervoort, Stephin J, Tan, Sander C, Mijnheer, Gerdien, de Roock, Sytze, Vastert, Sebastiaan J., Nieuwenhuis, Edward E S, van Wijk, Femke, Prakken, Berent J, Creyghton, Menno P, Coffer, Paul J, Mokry, Michal, van Loosdregt, Jorg, CMM Groep Coffer, CTI Van Wijk, Infection & Immunity, CTI Van Loosdregt, Child Health, Immuno/reuma onderzoek 1 (Vastert), Reumatologie patientenzorg, Zorg en O&O, Regenerative Medicine and Stem Cells, Circulatory Health, CTI Vastert, Reumatologie onderzoek 2, Hubrecht Institute with UMC, Immunologie onderzoek 2, Cancer, MDL onderzoek 3, Peeters, Janneke G C, Vervoort, Stephin J, Tan, Sander C, Mijnheer, Gerdien, de Roock, Sytze, Vastert, Sebastiaan J., Nieuwenhuis, Edward E S, van Wijk, Femke, Prakken, Berent J, Creyghton, Menno P, Coffer, Paul J, Mokry, Michal, and van Loosdregt, Jorg

Published
2015

17. Site-Specific Chemoenzymatic Labeling of Aerolysin Enables the Identification of New Aerolysin Receptors

Author

Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemistry, Whitehead Institute for Biomedical Research, Wuethrich, Irene, Peeters, Janneke G. C., Blom, Annet E. M., Li, Zeyang, Spooner, Eric, Theile, Christopher S., Ploegh, Hidde, Guimaraes, Carla P., Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemistry, Whitehead Institute for Biomedical Research, Wuethrich, Irene, Peeters, Janneke G. C., Blom, Annet E. M., Li, Zeyang, Spooner, Eric, Theile, Christopher S., Ploegh, Hidde, and Guimaraes, Carla P.

Abstract

Aerolysin is a secreted bacterial toxin that perforates the plasma membrane of a target cell with lethal consequences. Previously explored native and epitope-tagged forms of the toxin do not allow site-specific modification of the mature toxin with a probe of choice. We explore sortase-mediated transpeptidation reactions (sortagging) to install fluorophores and biotin at three distinct sites in aerolysin, without impairing binding of the toxin to the cell membrane and with minimal impact on toxicity. Using a version of aerolysin labeled with different fluorophores at two distinct sites we followed the fate of the C-terminal peptide independently from the N-terminal part of the toxin, and show its loss in the course of intoxication. Making use of the biotinylated version of aerolysin, we identify mesothelin, urokinase plasminogen activator surface receptor (uPAR, CD87), glypican-1, and CD59 glycoprotein as aerolysin receptors, all predicted or known to be modified with a glycosylphosphatidylinositol anchor. The sortase-mediated reactions reported here can be readily extended to other pore forming proteins., National Institutes of Health (U.S.) (grant R01 AI087879)

Published
2014

19. Epstein-Barr Virus Large Tegument Protein BPLF1 Contributes to Innate Immune Evasion through Interference with Toll-Like Receptor Signaling

Author

van Gent, Michiel, primary, Braem, Steven G. E., additional, de Jong, Annemieke, additional, Delagic, Nezira, additional, Peeters, Janneke G. C., additional, Boer, Ingrid G. J., additional, Moynagh, Paul N., additional, Kremmer, Elisabeth, additional, Wiertz, Emmanuel J., additional, Ovaa, Huib, additional, Griffin, Bryan D., additional, and Ressing, Maaike E., additional

Published
2014
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20. Site-Specific Chemoenzymatic Labeling of Aerolysin Enables the Identification of New Aerolysin Receptors

Author

Irene Wuethrich, Hidde L. Ploegh, Christopher S. Theile, Janneke G. C. Peeters, Eric Spooner, Zeyang Li, Annet E M Blom, Carla P. Guimaraes, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemistry, Whitehead Institute for Biomedical Research, Wuethrich, Irene, Peeters, Janneke G. C., Blom, Annet E. M., Li, Zeyang, Spooner, Eric, Theile, Christopher S., Ploegh, Hidde, and Guimaraes, Carla P.

Subjects
Cell Membranes, lcsh:Medicine, Pathogenesis, Bioinformatics, Toxicology, Pathology and Laboratory Medicine, Biochemistry, Cell membrane, Molecular Cell Biology, Toxin Binding, Medicine and Health Sciences, lcsh:Science, Peptide sequence, chemistry.chemical_classification, Multidisciplinary, Optical Imaging, 3. Good health, Aeromonas hydrophila, Bacterial Pathogens, medicine.anatomical_structure, Medical Microbiology, Biotinylation, Host-Pathogen Interactions, Cellular Structures and Organelles, Pathogens, Research Article, Pore Forming Cytotoxic Proteins, Bacterial Toxins, Molecular Sequence Data, Aerolysin, Biotin, CD59 Antigens, Biology, Microbiology, Cell Line, Receptors, Urokinase Plasminogen Activator, Glypicans, medicine, Animals, Humans, Amino Acid Sequence, Protein Interactions, Urokinase Plasminogen Activator Surface Receptor, Microbial Pathogens, Molecular Biology, Fluorescent Dyes, lcsh:R, Biology and Life Sciences, Proteins, Membrane Proteins, Cell Biology, Urokinase receptor, chemistry, Membrane protein, lcsh:Q, Glycoprotein, Membrane Characteristics
Abstract

Aerolysin is a secreted bacterial toxin that perforates the plasma membrane of a target cell with lethal consequences. Previously explored native and epitope-tagged forms of the toxin do not allow site-specific modification of the mature toxin with a probe of choice. We explore sortase-mediated transpeptidation reactions (sortagging) to install fluorophores and biotin at three distinct sites in aerolysin, without impairing binding of the toxin to the cell membrane and with minimal impact on toxicity. Using a version of aerolysin labeled with different fluorophores at two distinct sites we followed the fate of the C-terminal peptide independently from the N-terminal part of the toxin, and show its loss in the course of intoxication. Making use of the biotinylated version of aerolysin, we identify mesothelin, urokinase plasminogen activator surface receptor (uPAR, CD87), glypican-1, and CD59 glycoprotein as aerolysin receptors, all predicted or known to be modified with a glycosylphosphatidylinositol anchor. The sortase-mediated reactions reported here can be readily extended to other pore forming proteins., National Institutes of Health (U.S.) (grant R01 AI087879)

Published
2014

21. Hyperactivating EZH2 to augment H3K27me3 levels in regulatory T cells enhances immune suppression by driving early effector differentiation.

Author

Peeters JGC, Silveria S, Ozdemir M, Ramachandran S, and DuPage M

Subjects
Animals, Mice, Autoimmunity, Mice, Inbred C57BL, CD28 Antigens metabolism, Methylation, Enhancer of Zeste Homolog 2 Protein metabolism, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, Cell Differentiation, Histones metabolism
Abstract

The immunosuppressive function of regulatory T (Treg) cells is essential for maintaining immune homeostasis. Enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 (H3K27) methyltransferase, plays a key role in maintaining Treg cell function upon CD28 co-stimulation, and Ezh2 deletion in Treg cells causes autoimmunity. Here, we assess whether increasing H3K27me3 levels, by using an Ezh2 Y641F gain-of-function mutation, will improve Treg cell function. We find that Treg cells expressing Ezh2 Y641F display an effector Treg phenotype, are poised for improved homing to organ tissues, and can accelerate remission from autoimmunity. The H3K27me3 landscape and transcriptome of naive Ezh2 Y641F Treg cells exhibit a redistribution of H3K27me3 modifications that recapitulates the gene expression profile of activated Ezh2 WT Treg cells after CD28 co-stimulation. Altogether, increased H3K27me3 levels promote the differentiation of effector Treg cells that can better suppress autoimmunity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2024
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22. Increased EZH2 function in regulatory T cells promotes their capacity to suppress autoimmunity by driving effector differentiation prior to activation.

Author

Peeters JGC, Silveria S, Ozdemir M, Ramachandran S, and DuPage M

Abstract

The immunosuppressive function of regulatory T (Treg) cells is essential for maintaining immune homeostasis. Enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 (H3K27) methyltransferase, plays a key role in maintaining Treg cell function upon CD28 co-stimulation, and Ezh2 deletion in Treg cells causes autoimmunity. Here we assessed whether increased EZH2 activity in Treg cells would improve Treg cell function. Using an Ezh2 gain-of-function mutation, Ezh2 Y641F , we found that Treg cells expressing Ezh2 Y641F displayed an increased effector Treg phenotype and were poised for improved homing to organ tissues. Expression of Ezh2 Y641F in Treg cells led to more rapid remission from autoimmunity. H3K27me3 profiling and transcriptomic analysis revealed a redistribution of H3K27me3, which prompted a gene expression profile in naïve Ezh2 Y641F Treg cells that recapitulated aspects of CD28-activated Ezh2 WT Treg cells. Altogether, increased EZH2 activity promotes the differentiation of effector Treg cells that can better suppress autoimmunity., Highlights: EZH2 function promotes effector differentiation of Treg cells.EZH2 function promotes Treg cell migration to organ tissues.EZH2 function in Treg cells improves remission from autoimmunity.EZH2 function poises naïve Treg cells to adopt a CD28-activated phenotype.

Published
2024
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23. Autoimmune disease-associated gene expression is reduced by BET-inhibition.

Author

Peeters JG, Vervoort SJ, Mijnheer G, de Roock S, Vastert SJ, Nieuwenhuis EE, van Wijk F, Prakken BJ, Mokry M, and van Loosdregt J

Abstract

For many autoimmune diseases, the underlying mechanism is still unknown. In order to get more insight into the etiology of autoimmune diseases, we recently published a study were we performed epigenetic profiling and RNA sequencing on CD4(+)CD45RO(+) T cells derived from the site of inflammation of Juvenile Idiopathic Arthritis (JIA) patients and compared this with healthy controls [1]. In this "Data in Brief", we focus on the analysis of our RNA sequencing data reported in this study, of which the raw and processed files can be found in GEO under GSE71595. We provide a detailed description of the downstream analysis, quality controls, and different analysis methods or techniques that validate the results obtained with RNA-sequencing.

Published
2015
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24. Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression.

Author

Peeters JG, Vervoort SJ, Tan SC, Mijnheer G, de Roock S, Vastert SJ, Nieuwenhuis EE, van Wijk F, Prakken BJ, Creyghton MP, Coffer PJ, Mokry M, and van Loosdregt J

Subjects
Arthritis, Juvenile genetics, Arthritis, Juvenile metabolism, Arthritis, Juvenile pathology, Autoimmunity, Base Sequence, Chemokine CXCL12 genetics, Chemokine CXCL12 metabolism, Core Binding Factor Alpha 2 Subunit genetics, Core Binding Factor Alpha 2 Subunit metabolism, Cytokines genetics, Cytokines metabolism, Enhancer Elements, Genetic drug effects, Epigenesis, Genetic, High-Throughput Nucleotide Sequencing, Humans, Immunologic Memory, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear metabolism, Leukocytes, Mononuclear pathology, Molecular Sequence Data, Primary Cell Culture, Proto-Oncogene Protein c-ets-1 genetics, Proto-Oncogene Protein c-ets-1 metabolism, Proto-Oncogene Proteins antagonists & inhibitors, Proto-Oncogene Proteins metabolism, Receptors, Cytokine genetics, Receptors, Cytokine metabolism, Signal Transduction, Synovial Fluid cytology, Synovial Fluid drug effects, Synovial Fluid metabolism, T-Lymphocytes metabolism, T-Lymphocytes pathology, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Arthritis, Juvenile drug therapy, Azepines pharmacology, Proto-Oncogene Proteins genetics, T-Lymphocytes drug effects, Triazoles pharmacology
Abstract

The underlying molecular mechanisms for many autoimmune diseases are poorly understood. Juvenile idiopathic arthritis (JIA) is an exceptionally well-suited model for studying autoimmune diseases due to its early onset and the possibility to analyze cells derived from the site of inflammation. Epigenetic profiling, utilizing primary JIA patient-derived cells, can contribute to the understanding of autoimmune diseases. With H3K27ac chromatin immunoprecipitation, we identified a disease-specific, inflammation-associated, typical enhancer and super-enhancer signature in JIA patient synovial-fluid-derived CD4(+) memory/effector T cells. RNA sequencing of autoinflammatory site-derived patient T cells revealed that BET inhibition, utilizing JQ1, inhibited immune-related super-enhancers and preferentially reduced disease-associated gene expression, including cytokine-related processes. Altogether, these results demonstrate the potential use of enhancer profiling to identify disease mediators and provide evidence for BET inhibition as a possible therapeutic approach for the treatment of autoimmune diseases., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2015
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