Retinoic acid can enhance conversion of naive into regulatory T cells independently of secreted cytokines.
Retinoic acid can enhance conversion of naive into regulatory T cells independently of secreted cytokines.
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DOI：
10.1084/jem.20090639
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发表时间：
2009-09-28
期刊：
影响因子：
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通讯作者：
von Boehmer H
中科院分区：
文献类型：
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作者：
Nolting J;Daniel C;Reuter S;Stuelten C;Li P;Sucov H;Kim BG;Letterio JJ;Kretschmer K;Kim HJ;von Boehmer H
据报道，视黄酸（RA）通过抑制干扰转化的细胞因子的分泌来增强调节性T（T reg）细胞转化。本报告表明，这些结论充其量只能提供部分解释。首先，RA不仅干扰细胞因子分泌，而且还干扰这些细胞因子抑制初始T细胞的T reg细胞转化的能力。此外，即使在没有抑制性细胞因子的情况下，RA也能增强转化。后者的作用依赖于RA受体α（RARα），但不需要Smad 3，尽管RA增强Smad 3的表达。RARα1亚型对于RA依赖性增强转化生长因子β驱动的转化不是必需的，表明转化也可以由RARα2介导。白细胞介素（IL）-6强烈降低RARα表达水平，使得主要RARα1同种型的缺陷使得RA在IL-6存在下抑制Th 17细胞生成的RARα2太少。
It has been reported that retinoic acid (RA) enhances regulatory T (T reg) cell conversion by inhibiting the secretion of cytokines that interfere with conversion. This report shows that these conclusions provide a partial explanation at best. First, RA not only interfered with cytokine secretion but also with the ability of these cytokines to inhibit T reg cell conversion of naive T cells. Furthermore, RA enhanced conversion even in the absence of inhibitory cytokines. The latter effect depended on the RA receptor α (RARα) but did not require Smad3, despite the fact that RA enhanced Smad3 expression. The RARα1 isoform was not essential for RA-dependent enhancement of transforming growth factor β–driven conversion, suggesting that conversion can also be mediated by RARα2. Interleukin (IL)-6 strongly reduced RARα expression levels such that a deficiency of the predominant RARα1 isoform leaves too little RARα2 for RA to inhibit the generation of Th17 cells in the presence of IL-6.