PDF(Pubmed)
Abstract：
Innate immune cells, including macrophages, are functionally affected by thyroid hormone (TH). Macrophages can undergo phenotypical alterations, shifting between proinflammatory (M1) and immunomodulatory (M2) profiles. Cellular TH concentrations are, among others, determined by TH transporters. To study the effect of TH and TH transporters on macrophage polarization, specific proinflammatory and immunomodulatory markers were analyzed in bone marrow-derived macrophages (BMDMs) depleted of triiodothyronine (T3) and BMDMs with a knockout (KO) of Mct8 and Mct10 and a double KO (dKO) of Mct10/Mct8. Our findings show that T3 is important for M1 polarization, while a lack of T3 stimulates M2 polarization. Mct8 KO BMDMs are unaffected in their T3 responsiveness, but exhibit slight alterations in M2 polarization, while Mct10 KO BMDMs show reduced T3 responsiveness, but unaltered polarization markers. KO of both the Mct8 and Mct10 transporters decreased T3 availability and, contrary to the T3-depleted BMDMs, showed partially increased M1 markers and unaltered M2 markers. These data suggest a role for TH transporters besides transport of TH in BMDMs. This study highlights the complex role of TH transporters in macrophages and provides a new angle on the interaction between the endocrine and immune systems.
摘要：
先天性免疫细胞，包括巨噬细胞,在功能上受到甲状腺激素（TH）的影响。巨噬细胞可以经历表型改变，促炎（M1）和免疫调节（M2）谱之间的转换。细胞TH浓度是，其中,由TH运输商确定。研究TH和TH转运体对巨噬细胞极化的影响,在缺失三碘甲状腺原氨酸(T3)的骨髓源性巨噬细胞(BMDMs)和Mct8和Mct10基因敲除(KO)以及Mct10/Mct8的双重KO(dKO)的BMDMs中分析了特异性促炎和免疫调节标志物.我们的发现表明T3对于M1极化很重要，而缺乏T3刺激M2极化。Mct8KOBMDM的T3响应能力不受影响，但表现出M2极化的轻微变化，而Mct10KOBMDM显示降低的T3响应性，但没有改变的极化标记.Mct8和Mct10转运蛋白的KO都降低了T3的可用性，与T3耗尽的BMDM相反，显示部分增加的M1标记和未改变的M2标记。这些数据表明TH转运蛋白在BMDMs中除了转运外还起着作用。这项研究强调了TH转运蛋白在巨噬细胞中的复杂作用，并为内分泌系统和免疫系统之间的相互作用提供了一个新的角度。
