Activation of retinoic acid receptor-α favours regulatory T cell induction at the expense of IL-17-secreting T helper cell differentiation
✍ Scribed by Felix Schambach; Michael Schupp; Mitchell A. Lazar; Steven L. Reiner
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 126 KB
- Volume
- 37
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
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‐β. We now show that, in the context of TGF‐β 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‐α (RARα). 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 RARα could, therefore, be considered candidates for the treatment of autoimmunity.