Title

Regulation of Intracellular Triiodothyronine Is Essential for Optimal Macrophage Function.

Document Type

Article

Publication Date

5-1-2018

Institution/Department

Center for Molecular Medicine, Maine Medical Center Research Institute

Journal Title

Endocrinology

MeSH Headings

Animals, Cell Differentiation, Cytokines, Embryo, Nonmammalian, Gene Knockdown Techniques, Immunity, Innate, Inflammation, Iodide Peroxidase, Macrophages, Meningitis, Pneumococcal, Mice, Mice, Knockout, Mortality, Phagocytosis, Receptors, Thyroid Hormone, Thyroid Hormone Receptors alpha, Triiodothyronine, Zebrafish

Abstract

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, TRα, 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 TRα. This study provides important insights into the link between the endocrine and innate immune system.

ISSN

1945-7170

First Page

2241

Last Page

2252

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