Targeting the immune epigenome in Crohn’s disease

Research output: PhD ThesisPhd-Thesis - Research and graduation internal


Intestinal mononuclear myeloid cells (MMCs), which include macrophages and dendritic cells (DC), arise essentially from blood circulating monocytes and play a critical role in maintaining the homeostasis of the intestinal epithelium and healing, but are also involved as critical contributors to Crohn’s disease (CD) pathogenesis. These opposing events are linked to the capacity of MMCs to deal with different functional properties in response to diverse environmental stimuli. Epigenetic processes play an important role in the regulation of MMC differentiation and gene expression, mediated for instance by DNA methylation and histone post-translational modifications. Over the past decades, accumulating pieces of evidence have demonstrated that an aberrant epigenome in MMCs significantly contributes to the development of inflammatory diseases including CD. Thus, the immune-epigenome has become a promising field for finding new therapeutic targets, and biomarkers to improve diagnosis, prognosis, and drug response in inflammatory bowel diseases (IBD). Among the wide diversity of possible epigenetic targets, in this thesis, we focused on DNA CpG methylation, histone deacetylase (HDAC) enzymes and bromodomain (Brd)-containing proteins (BCPs), remodelers of histone tails, which play a central role in regulating inducible gene expression involved in immune response. We investigated the therapeutic potential of targeting the immune-epigenome, focusing on MMCs and inflammatory bowel disease (IBD), as well as exploring the possible existence of differential DNA methylome as a putative biomarker associated with different clinical activity in Crohn’s disease (CD) patients.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Amsterdam
  • de Jonge, Wouter, Supervisor
  • de Winther, Menno, Supervisor
  • te Velde, Anje A., Co-supervisor
  • Henneman, Peter, Co-supervisor
Award date14 Sept 2022
Print ISBNs9789464239522
Publication statusPublished - 2022

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