TY - JOUR
T1 - Regulation of intracellular triiodothyronine is essential for optimal macrophage function
AU - van der Spek, Anne H.
AU - Surovtseva, Olga V.
AU - Jim, Kin Ki
AU - van Oudenaren, Adri
AU - Brouwer, Matthijs C.
AU - Vandenbroucke-Grauls, Christina M. J. E.
AU - Leenen, Pieter J. M.
AU - van de Beek, Diederik
AU - Hernandez, Arturo
AU - Fliers, Eric
AU - Boelen, Anita
PY - 2018
Y1 - 2018
N2 - 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, TRa, 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 TRa. This study provides important insights into the link between the endocrine and innate immune system.
AB - 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, TRa, 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 TRa. This study provides important insights into the link between the endocrine and innate immune system.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85051989058&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29648626
U2 - 10.1210/en.2018-00053
DO - 10.1210/en.2018-00053
M3 - Article
C2 - 29648626
VL - 159
SP - 2241
EP - 2252
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 5
ER -