The Thyroid Hormone Triiodothyronine Controls Macrophage Maturation and Functions Protective Role during Inflammation

The endocrine system participates in regulating macrophage maturation, although little is known about the modulating role of the thyroid hormones. In vitro results demonstrate a negative role of one such hormone, triiodothyronine (T 3 ), in triggering the differentiation of bone marrow–derived monocytes into unpolarized macrophages. T 3 -induced macrophages displayed a classically activated (M1) signature. A T 3 -induced M1-priming effect was also observed on polarized macrophages because T 3 reverses alternatively activated (M2) activation, whereas it enhances that of M1 cells. In vivo , circulating T 3 increased the content of the resident macrophages in the peritoneal cavity, whereas it reduced the content of the recruited monocyte-derived cells. Of interest, T 3 significantly protected mice against endotoxemia induced by lipopolysaccharide i.p. injection; in these damaged animals, decreased T 3 levels increased the recruited (potentially damaging) cells, whereas restoring T 3 levels decreased recruited and increased resident (potentially beneficial) cells. These data suggest that the anti-inflammatory effect of T 3 is coupled to the modulation of peritoneal macrophage content, in a context not fully explained by the M1/M2 framework. Thyroid hormone receptor expression analysis and the use of different thyroid hormone receptor antagonists suggest thyroid hormone receptor β1 as the major player mediating T 3 effects on macrophages. The novel homeostatic link between thyroid hormones and the pathophysiological role of macrophages opens new perspectives on the interactions between the endocrine and immune systems.