The thyroid hormone triiodothyronine controls macrophage maturation and functions: Protective role during inflammation

Cristiana Perrotta, Marcella Buldorini, Emma Assi, Denise Cazzato, Clara De Palma, Emilio Clementi, Davide Cervia

Research output: Contribution to journalArticlepeer-review

Abstract

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 T 3 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 T 3 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.

Original languageEnglish
Pages (from-to)230-247
Number of pages18
JournalAmerican Journal of Pathology
Volume184
Issue number1
DOIs
Publication statusPublished - Jan 2014

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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