The Thyroid Hormone Inactivating Enzyme Type 3 Deiodinase is Present in Bactericidal Granules and the Cytoplasm of Human Neutrophils
Open accessAbstract
Neutrophils are important effector cells of the innate immune system. Thyroid hormone (TH) is thought to play an important role in their function. Intracellular TH levels are regulated by the deiodinating enzymes. The TH-inactivating type 3 deiodinase (D3) is expressed in infiltrating murine neutrophils, and D3 knockout mice show impaired bacterial killing upon infection. This suggests that D3 plays an important role in the bacterial killing capacity of neutrophils. The mechanism behind this effect is unknown. We aimed to assess the presence of D3 in human neutrophils, and determine its subcellular localization using confocal and electron microscopy, because this could give important clues about its function in these cells. D3 appeared to be present in the cytoplasm and in myeloperoxidase containing azurophilic granules and as well as lactoferrin containing specific granules within human neutrophils. This subcellular localization did not change upon activation of the cells. D3 is observed intracellularly during neutrophil extracellular trap formation, followed by a reduction of D3 staining after release of the neutrophil extracellular traps into the extracellular space. At the transcriptional level, human neutrophils expressed additional essential elements of TH metabolism, including TH transporters and TH receptors. Here, we demonstrate the presence and subcellular location of D3 in human neutrophils for the first time and propose a model, in which D3 plays a role in the bacterial killing capacity of neutrophils either through generation of iodide for the myeloperoxidase system or through modulation of intracellular TH bioavailability.
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DIO3 is expressed in human neutrophils and present in intracellular granules involved in bacterial killing and in neutrophil extracellular traps (NETs).
“DIO3 is also expressed in human neutrophils [34] and present in intracellular granules involved in bacterial killing and in neutrophil extracellular traps (NETs) [34].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [34]
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Self-citation
- Authors
- van der Spek, A. H., Bloise, F. F., Tigchelaar, W., Dentice, M., Salvatore, D., van der Wel, N. N., Fliers, E., & Boelen, A.
- Affiliations
- Department of Endocrinology and Metabolism (A.H.v.d.S., F.F.B., E.F., A.B.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
- Amsterdam UMC Location University of Amsterdam (NL)
- Federico II University Hospital (IT)
- Department of Cell Biology and Histology (W.T., N.N.v.d.W.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2016-06-29
- Volume
- 157
- Issue
- 8
- Pages
- 3293-3305
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2469279603
- Cited by
- 28
- References
- 90
- Citations by year
- 2026: 2 · 2025: 3 · 2022: 4 · 2021: 1 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 6 · 2016: 1
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- thyroid hormones, type 3 deiodinase, neutrophils, bacterial killing, azurophilic granules, lactoferrin, neutrophil extracellular traps, myeloperoxidase, subcellular localization, innate immunity, thyroid hormone transporters, thyroid hormone receptor, neutrophil activation
- MeSH terms
- Anti-Bacterial Agents, Cells, Cultured, Cytoplasm, Cytoplasmic Granules, Female, Humans, Iodide Peroxidase, Male, Neutrophils, Endosomes, Thyroid Hormones, Tissue Distribution, Extracellular Traps
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