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Publication : Regulation of Intracellular Triiodothyronine Is Essential for Optimal Macrophage Function.

First Author  van der Spek AH Year  2018
Journal  Endocrinology Volume  159
Issue  5 Pages  2241-2252
PubMed ID  29648626 Mgi Jnum  J:261405
Mgi Id  MGI:6155439 Doi  10.1210/en.2018-00053
Citation  van der Spek AH, et al. (2018) Regulation of Intracellular Triiodothyronine Is Essential for Optimal Macrophage Function. Endocrinology 159(5):2241-2252
abstractText  Innate immune cells, including macrophages, have recently been identified as target cells for thyroid hormone. We hypothesized that optimal intracellular concentrations of the active thyroid hormone triiodothyronine (T3) are essential for proinflammatory 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 D2 knockout 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, TRalpha, impaired polarization into proinflammatory macrophages and amplified polarization into immunomodulatory 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 TRalpha. This study provides important insights into the link between the endocrine and innate immune system.
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