Epitranscriptomic regulation in immunity and autoimmune disease: Unraveling novel implications of RNA modification m6A

Ellen van Vroonhoven

Research output: ThesisDoctoral thesis 1 (Research UU / Graduation UU)

Abstract

The immune system protects the human body against pathogens such as viruses, bacteria, and parasites. It has innate and acquired components, which together recognize and eliminate these threats. When the immune system mistakes the body's own materials for pathogens, autoimmune diseases can occur.

Immune cells, including T-helper cells (CD4+ T cells) and monocytes, play crucial roles in pathogen recognition, immune activation, and signaling molecule production. T-helper cells activate other immune cells through co-activation molecules like ICOS, CD28, and CD40L, while monocytes are involved in phagocytosis and regulating immune responses.

RNA molecules labeled with m6A modification are key in regulating immune cell function. Proteins such as FTO and METTL3 modulate the presence of m6A on RNA, influencing gene expression and immune activation. m6A modifications impact the production and secretion of signaling molecules like TNF, which are critical in immune responses and autoimmune diseases.

Research detailed in this thesis highlights the importance of m6A in:
- Activating T-helper cells by regulating CD40L expression.
- Modulating TNF production in T-helper cells and monocytes.
- Controlling immune cell activation and antiviral responses against respiratory syncytial virus (RSV).
- Influencing autoimmune diseases like juvenile idiopathic arthritis through altered expression of FTO and m6A labeling.

These findings offer potential therapeutic targets for treating immune-related diseases and viral infections by manipulating m6A-regulating proteins.
Original languageEnglish
Awarding Institution
  • University Medical Center (UMC) Utrecht
Supervisors/Advisors
  • van Loosdregt, Jorg, Supervisor
  • Vastert, Bas, Primary supervisor
Award date4 Feb 2025
Place of PublicationUtrecht
Publisher
DOIs
Publication statusPublished - 4 Feb 2025

Keywords

  • RNA methylation
  • epitranscriptomics
  • CD40 ligand
  • T cell activation
  • immunity
  • autoimmunity
  • tumor necrosis factor
  • monocyte activation
  • respiratory syncytial virus
  • Juvenile Idiopathic Arthritis

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