A.H. van der Spek
- The role of intracellular thyroid hormone metabolism in innate immune cells
- Award date
- 27 June 2018
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
Innate immune cells have recently been identified as important thyroid hormone target cells. This thesis studies the role of intracellular thyroid hormone metabolism in the function of neutrophils and macrophages, two essential cell types of the innate immune system.
Neutrophils, monocytes and precursor cells all derived from mouse bone marrow, contain different elements of intracellular thyroid hormone metabolism. The thyroid hormone inactivating enzyme type 3 deiodinase (D3) is present in neutrophils and appears to play an important role in their function during bacterial killing. A lack of D3 resulted in impaired neutrophil function both in neutrophils derived from D23 knockout mice and in a zebrafish model for bacterial meningitis. This suggests that low concentrations of intracellular thyroid hormone are beneficial to pro-inflammatory neutrophil function.
In macrophages, low intracellular thyroid hormone concentrations and action appears to have an opposite effect. A lack of the thyroid hormone activating enzyme type 2 deiodinase (D2), impairs pro-inflammatory function in a macrophage cell line and bone marrow derived macrophages. By knocking down the main thyroid hormone receptor in macrophages, TRα, macrophages’ ability to adopt a pro-inflammatory phenotype is reduced. These results suggest that, contrary to neutrophils, reduced intracellular thyroid hormone action skews macrophages towards a more anti-inflammatory phenotype.
This data shows that strict regulation of intracellular thyroid hormone action is essential for neutrophil and macrophage function.
Thesis (complete) (Embargo up to and including 27 June 2019)
Chapter 2: Intracellular thyroid hormone metabolism in neutrophils and monocytes (Embargo up to and including 27 June 2019)
Chapter 5: The thyroid hormone inactivating type 3 deiodinase is essential for optimal neutrophil function: Observations from 3 species (Embargo up to and including 27 June 2019)
Chapter 7: Regulation of intracellular triiodothyronine is essential for optimal macrophage function (Embargo up to and including 27 June 2019)
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