ZFIN ID: ZDB-PUB-180418-27
Regulation of Intracellular Triiodothyronine is Essential for Optimal Macrophage Function
van der Spek, A.H., Surovtseva, O.V., Jim, K.K., van Oudenaren, A., Brouwer, M.C., Vandenbroucke-Grauls, C.M.J.E., Leenen, P.J.M., van de Beek, D., Hernandez, A., Fliers, E., Boelen, A.
Date: 2018
Source: Endocrinology   159(5): 2241-2252 (Journal)
Registered Authors:
Keywords: none
MeSH Terms:
  • Animals
  • Cell Differentiation
  • Cytokines/immunology
  • Embryo, Nonmammalian/metabolism*
  • Gene Knockdown Techniques
  • Immunity, Innate/immunology
  • Inflammation
  • Iodide Peroxidase/genetics*
  • Macrophages/immunology
  • Macrophages/metabolism*
  • Meningitis, Pneumococcal/immunology
  • Meningitis, Pneumococcal/mortality
  • Mice
  • Mice, Knockout
  • Mortality
  • Phagocytosis/immunology
  • Receptors, Thyroid Hormone/genetics
  • Thyroid Hormone Receptors alpha/genetics*
  • Triiodothyronine/immunology
  • Triiodothyronine/metabolism*
  • Zebrafish
PubMed: 29648626 Full text @ Endocrinology
Innate immune cells, including macrophages, have recently been identified as novel target cells for thyroid hormone. We hypothesized that optimal intracellular concentrations of the active thyroid hormone triiodothyronine (T3) are essential for pro-inflammatory macrophage function. T3 is generated intracellularly by type 2 deiodinase (D2) and acts via the nuclear thyroid hormone receptor (TR). In zebrafish embryos, D2 knockdown increased mortality during pneumococcal meningitis. Primary murine D2KO macrophages exhibited impaired phagocytosis and partially reduced cytokine response to stimulation with bacterial endotoxin. These effects are presumably due to reduced intracellular T3 availability. Knockdown of the main TR in macrophages, TRα, impaired polarization into pro-inflammatory (M(LPS+IFNγ)) macrophages and amplified polarization into immunomodulatory (M(IL-4)) macrophages. Intracellular T3 availability and action appear to play a crucial role in macrophage function. Our data suggest that low intracellular T3 action has an anti-inflammatory effect, possibly due to an effect on macrophage polarization mediated via the TRα. This study provides important novel insights into the link between the endocrine and innate immune system.