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 (T3), in triggering the differentiation of bone marrow-derived monocytes into unpolarized macrophages. T3-induced macrophages displayed a classically activated (M1) signature. A T3-induced M1-priming effect was also observed on polarized macrophages because T3 reverses alternatively activated (M2) activation, whereas it enhances that of M1 cells. In vivo, circulating T3 increased the content of the resident macrophages in the peritoneal cavity, whereas it reduced the content of the recruited monocyte-derived cells. Of interest, T3 significantly protected mice against endotoxemia induced by lipopolysaccharide i.p. injection; in these damaged animals, decreased T3 levels increased the recruited (potentially damaging) cells, whereas restoring T3 levels decreased recruited and increased resident (potentially beneficial) cells. These data suggest that the anti-inflammatory effect of T3 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 T3 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.
|Titolo:||The thyroid hormone triiodothyronine controls macrophage maturation and functions : protective role during inflammation|
|Parole Chiave:||Animals; Blotting, Western; Cell Differentiation; Cells, Cultured; Female; Flow Cytometry; Immunophenotyping; Inflammation; Macrophage Activation; Macrophages; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Triiodothyronine|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
Settore MED/04 - Patologia Generale
|Data di pubblicazione:||gen-2014|
|Digital Object Identifier (DOI):||10.1016/j.ajpath.2013.10.006|
|Appare nelle tipologie:||01 - Articolo su periodico|