Balancing macrophage activation in health and disease: The epigenetic, transcriptional and immunometabolic insights

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

Abstract

Macrophages are crucial components of the innate immune system. Macrophages manifest extreme heterogeneity in response to the local milieu. The plasticity and diversity of macrophages are pivotal for host defense against pathogenic insults and the maintenance of tissue homeostasis. However, dysregulated macrophage activation can lead to acute and chronic inflammatory disorders, such as COVID-19, atherosclerosis, and inflammatory bowel diseases. The activation states of macrophages are shaped by various mechanisms, such as epigenetic modifications, transcriptional regulation, and metabolic alterations. This dissertation provides comprehensive transcriptomic and metabolomic profiles of widely used macrophage models. We build a macrophage activation classifier and identify key regulatory network modules constructed by unbiased approaches. Furthermore, our data delivers insights into targeting metabolic pathways, kinases, and epigenetic enzymes for therapeutic development against various diseases. These findings advance our knowledge in macrophage activation and pathogenesis of different diseases and disorders that can support future studies from basic science to translational medicine and from bench to bedside.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Amsterdam
Supervisors/Advisors
  • de Winther, Menno, Supervisor
  • de Jonge, Wouter, Supervisor
  • Henneman, Peter, Co-supervisor
  • Neele, Annette, Co-supervisor
Award date12 Oct 2022
Print ISBNs9789464586237
Publication statusPublished - 2022

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