Endocrine Abstracts

Macrophages are phagocytic immune cells with many functions, including fighting infections and wound healing. As a result, they are also involved in many diseases, such as metabolic syndrome, neurodegenerative disorders and cancer. Macrophages have been identified as thyroid hormone (TH) target cells, but the link between TH and the immune system is not yet fully understood. The active thyroid hormone triiodothyronine (T3) exerts its action through the nuclear thyroid hormone receptor (TR), of which the TRα is the dominant receptor in macrophages. The role of the TRα in macrophage function was investigated using bone marrow derived macrophages (BMDMs) from transgenic mice with a mutation in the T3 binding domain of the TRα (TRαPV, a dominant negative variant, resulting in resistance to thyroid hormone). BMDMs from these mice and corresponding wild types (WT) were polarized into a pro-inflammatory M1 or immunomodulatory M2 phenotype using either LPS + interferon gamma or IL-4 respectively. Pro- and anti-inflammatory cell surface marker expression was measured with flow cytometry. In addition, immunometabolism of the macrophages was measured using Seahorse analysis. The results of three consecutive cultures are described, further analyses are ongoing. After polarization into an M1 phenotype, expression of the M1 surface markers CD80 and CD86 decreased in TRαPV macrophages compared to WT macrophages, while the M2 cell surface marker CD206 showed an increasing trend in TRαPV M2 macrophages. Additionally, M2 TRαPV macrophages tend to increase their oxygen consumption, indicating increased oxidative phosphorylation, which is a hallmark of M2 macrophages. RNA sequencing analysis will be performed in order to unravel the molecular mechanisms involved. In conclusion, a dominant negative mutation of the TRα results in decreased pro-inflammatory marker expression in M1 cells, increased expression of an immunomodulatory marker in M2 cells, accompanied by elevated oxidative phosphorylation. These results indicate that impaired TRα function could alter macrophage phenotype and function.