Journal
CELL REPORTS
Volume 12, Issue 12, Pages 1986-1996Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2015.08.046
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Funding
- Dutch Arthritis Foundation
- Netherlands Organization for Scientific Research (NWO)
- Dutch Cancer Society (KWF) [UU 2013-5801]
- ReumaFonds [12-2-404] Funding Source: researchfish
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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.
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