Activation of retinoic acid receptor-α favours regulatory T cell induction at the expense of IL-17-secreting T helper cell differentiation
Activation of retinoic acid receptor-α favours regulatory T cell induction at the expense of IL-17-secreting T helper cell differentiation
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DOI：
10.1002/eji.200737621
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发表时间：
2007-09-01
影响因子：
5.4
通讯作者：
Reiner, Steven L.
中科院分区：
文献类型：
--
作者：
Schambach, Felix;Schupp, Michael;Reiner, Steven L.
自身免疫被认为反映了调节性T辅助淋巴细胞（Treg）和致病性IL-17分泌性T辅助（Th 17）细胞之间的失衡。适应性Treg和Th 17细胞的诱导需要来自TGF-β的信号传导。我们现在表明，在TGF-β信号传导的背景下，全反式维甲酸（ATRA）导致表达Treg特化因子叉头盒蛋白P3（FoxP 3）的CD 4（+）T细胞诱导增加，表达IL-17的细胞频率降低，即使在IL-6存在的情况下。使用特定的激动剂和拮抗剂，以及逆转录病毒的过度表达，我们还提供了证据表明，ATRA的影响可能至少部分由核视黄酸受体α（RAR α）介导。这些发现表明，通过特定的核视黄酸受体的信号传导可以有利于以Th 17命运为代价采用Treg命运的决定。因此，RAR α的特异性激动剂可以被认为是治疗自身免疫的候选药物。
Autoimmunity is thought to reflect an imbalance between regulatory T helper lymphocytes (Treg) and pathogenic, IL-17-secreting T helper (Th17) cells. Induction of both adaptive Treg and Th17 cells requires signalling from TGF-beta. We now show that, in the context of TGF-beta signalling, all-trans retinoic acid (ATRA) leads to increased induction of CD4(+) T cells expressing the Treg specification factor forkhead box protein P3 (FoxP3) and decreased frequency of cells expressing IL-17, even in the presence of IL-6. Using a specific agonist and antagonist, as well as retroviral over-expression, we also provide evidence that the effects of ATRA are likely to be at least partially mediated by the nuclear retinoic acid receptor-a, (RAR alpha). These findings indicate that signalling through a specific nuclear retinoic acid receptor can favour the decision to adopt the Treg fate at the expense of Th17 fate. Specific agonists of RAR alpha could, therefore, be considered candidates for the treatment of autoimmunity.