Retinoic Acid Can Enhance Conversion of Naive into Regulatory T Cells Independently of Secreted Cytokines
Letterio, John J.
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CitationNolting, Jens, Carolin Daniel, Sabine Reuter, Christina Stuelten, Peng Li, Henry Sucov, Byung-Gyu Kim, et al. 2009. Retinoic acid can enhance conversion of naive into regulatory T cells independently of secreted cytokines. The Journal of Experimental Medicine 206(10): 2131-2139.
AbstractIt 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.
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