Diminished Pro-Inflammatory Characteristics in Murine Bone Marrow Derived Macrophages with Impaired Thyroid Hormone Receptor Alpha 1 Signaling

Background: Macrophages are versatile phagocytes of the innate immune system with functions ranging from pro-inflammatory to immunomodulatory. Macrophages are receptive to signals from thyroid hormones (THs). Here, we studied the role of the TH receptor (TR)α1 in macrophage function. Methods: Using wild type (WT) and transgenic mice with a mutation in the T3 binding domain of the TRα1 (TRα1PV), we generated bone marrow derived macrophages (BMDMs) and subsequently polarized them into pro-inflammatory or immunomodulatory phenotypes. The phenotype and function of the unpolarized, pro-inflammatory and immunomodulatory TRα1PV BMDMs was compared with the respective WT BMDMs. Results: RNA sequencing revealed different expression profiles and alterations of biological pathways, including immune functions in all TRα1PV BMDM phenotypes. The pro-inflammatory TRα1PV BMDMs exhibited decreased marker expression associated with this phenotype, while marker expression of unpolarized and immunomodulatory TRα1PV BMDMs was unaltered. Glycolysis, a characteristic of pro-inflammatory macrophages, was reduced in all three TRα1PV macrophage phenotypes. Conclusions: Altogether, we observed that the TRα1PV mutation results in phenotypical and functional different BMDMs, with most striking changes in the pro-inflammatory phenotype, underlining the significance of adequate T3-TRα1 signaling in pro-inflammatory macrophage responses.