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Regulation of Intracellular Triiodothyronine Is Essential for Optimal Macrophage Function.

Endocrinology | 2018

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.

Pubmed ID: 29648626 RIS Download

Associated grants

  • Agency: NIMH NIH HHS, United States
    Id: R01 MH096050
  • Agency: NIGMS NIH HHS, United States
    Id: P20 GM103465
  • Agency: European Research Council, International
    Id: 281156
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK095908
  • Agency: NIGMS NIH HHS, United States
    Id: P30 GM103392

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Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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