- The biology of human innate lymphoid cells
- Award date
- 15 April 2016
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
In this thesis I performed studies to investigate the contribution of human innate lymphoid cells (ILCs) in maintaining the mucosal homeostasis, initiating and/or propagating inflammatory responses, but also - when not properly regulated - how these cells contribute to immunopathology.
First I describe a previously unidentified subset of the human ILC family that is enriched in type 1 inflammatory diseases, which we named ILC1. More specifically, I found that ILC1 accumulated in resection specimen from individuals that suffer from Crohn’s disease, and this accumulation inversely correlated with the decrease of ILC3. Mechanistically, I found that ILC1 could derive from ILC3 when exposed to specific inflammatory factors. Furthermore, I observed that the plasticity is a reversible process following inflammatory resolution, and explored their molecular mechanisms underlying this plasticity.
Next, I explored the factors that induce ILC2 activation, as well as the effector molecules that are produced by these cells. In addition I performed gain- and loss-of-function experiments, which revealed the intracellular signalling pathways that are essential for ILC2 effector functions. Finally, I asked the question whether the observed plasticity was restricted to ILC1 and ILC3, or whether ILC2 may also have a reversible transdifferentiation potential towards pro-inflammatory ILC1 when exposed to a type 1 inflammatory environment. To this end, I performed phenotypical and functional studies from resection specimen of individuals that suffer from COPD or polyps from individuals that suffer from allergic chronic rhinosinusitis. Finally, I performed antibody-mediated neutralisation studies in ILC1, ILC2 and ILC3 to explore their potential to manipulate this plasticity.
- Research conducted at: Universiteit van Amsterdam
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