The Differential Effect of a Shortage of Thyroid Hormone Compared with Knockout of Thyroid Hormone Transporters Mct8 and Mct10 on Murine Macrophage Polarization

Innate immune cells, including macrophages, are functionally affected by thyroid hormone (TH). Macrophages can undergo phenotypical alterations, shifting between proinflammatory (M1) and immunomodulatory (M2) profiles. Cellular TH concentrations are, among others, determined by TH transporters. To s...

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Bibliographic Details
Published in:International journal of molecular sciences 2024-02, Vol.25 (4), p.2111
Main Authors: Hoen, Esmée, Goossens, Franka M, Falize, Kim, Mayerl, Steffen, van der Spek, Anne H, Boelen, Anita
Format: Article
Language:English
Subjects:
Amino Acid Transport Systems, Neutral - genetics
Amino Acid Transport Systems, Neutral - metabolism
Amino acids
Animals
bone marrow-derived macrophages
Comparative analysis
Cytokines
Flow cytometry
Genes
Genotype & phenotype
Macrophages
Macrophages - metabolism
Mct10
Mct8
Mice
Monocarboxylic Acid Transporters - genetics
Symporters - genetics
Thyroid gland
thyroid hormone
thyroid hormone transporters
Thyroid hormones
Thyroid Hormones - metabolism
Thyroid Hormones - pharmacology
Triiodothyronine - pharmacology
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Summary:Innate immune cells, including macrophages, are functionally affected by thyroid hormone (TH). Macrophages can undergo phenotypical alterations, shifting between proinflammatory (M1) and immunomodulatory (M2) profiles. Cellular TH concentrations are, among others, determined by TH transporters. To study the effect of TH and TH transporters on macrophage polarization, specific proinflammatory and immunomodulatory markers were analyzed in bone marrow-derived macrophages (BMDMs) depleted of triiodothyronine (T3) and BMDMs with a knockout (KO) of Mct8 and Mct10 and a double KO (dKO) of Mct10/Mct8. Our findings show that T3 is important for M1 polarization, while a lack of T3 stimulates M2 polarization. Mct8 KO BMDMs are unaffected in their T3 responsiveness, but exhibit slight alterations in M2 polarization, while Mct10 KO BMDMs show reduced T3 responsiveness, but unaltered polarization markers. KO of both the Mct8 and Mct10 transporters decreased T3 availability and, contrary to the T3-depleted BMDMs, showed partially increased M1 markers and unaltered M2 markers. These data suggest a role for TH transporters besides transport of TH in BMDMs. This study highlights the complex role of TH transporters in macrophages and provides a new angle on the interaction between the endocrine and immune systems.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms25042111