Thyroid Hormone and Deiodination in Innate Immune Cells

Abstract

Abstract Thyroid hormone has recently been recognized as an important determinant of innate immune cell function. Highly specialized cells of the innate immune system, including neutrophils, monocytes/macrophages, and dendritic cells, are capable of identifying pathogens and initiating an inflammatory response. They can either phagocytose and kill microbes, or recruit other innate or adaptive immune cells to the site of inflammation. Innate immune cells derive from the hematopoietic lineage and are generated in the bone marrow, from where they can be recruited into the blood and tissues in the case of infection. The link between the immune and endocrine systems is increasingly well established, and recent studies have shown that innate immune cells can be seen as important thyroid hormone target cells. Tight regulation of cellular thyroid hormone availability and action is performed by thyroid hormone transporters, receptors, and the deiodinase enzymes. Innate immune cells express all these molecular elements of intracellular thyroid hormone metabolism. Interestingly, there is recent evidence for a causal relationship between cellular thyroid hormone status and innate immune cell function. This review describes the effects of modulation of intracellular thyroid hormone metabolism on innate immune cell function, specifically neutrophils, macrophages, and dendritic cells, with a special focus on the deiodinase enzymes. Although there are insufficient data at this stage for conclusions on the clinical relevance of these findings, thyroid hormone metabolism may partially determine the innate immune response and, by inference, the clinical susceptibility to infections.