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.
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机译:内分泌系统参与调节巨噬细胞的成熟,尽管对甲状腺激素的调节作用知之甚少。体外结果表明,一种这样的激素三碘甲状腺原氨酸(T3)在触发骨髓来源的单核细胞分化为非极化巨噬细胞方面具有负面作用。T3 诱导的巨噬细胞显示出经典激活 (M1) 特征。在极化巨噬细胞上也观察到 T3 诱导的 M1 引发效应,因为 T 3 逆转选择性激活 (M2) 激活,而增强 M1 细胞的激活。在体内,循环T3增加了腹膜腔中常驻巨噬细胞的含量,而降低了募集的单核细胞来源细胞的含量。有趣的是,T3显着保护小鼠免受脂多糖腹腔注射诱导的内毒素血症;在这些受损动物中,T3水平降低会增加募集(潜在损伤)细胞,而恢复T3水平会减少募集细胞并增加驻留(潜在有益)细胞。这些数据表明,在M1/M2框架无法完全解释的背景下,T3的抗炎作用与腹膜巨噬细胞含量的调节有关。甲状腺激素受体表达分析和不同甲状腺激素受体拮抗剂的使用表明甲状腺激素受体β1是介导巨噬细胞T3作用的主要参与者。甲状腺激素与巨噬细胞的病理生理作用之间的新型稳态联系为内分泌和免疫系统之间的相互作用开辟了新的视角。
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