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Retinoic acid can enhance conversion of naive into regulatory T cells independently of secreted cytokines

2009; Rockefeller University Press; Volume: 206; Issue: 10 Linguagem: Inglês

10.1084/jem.20090639

1540-9538

Jens Nolting, Carolin Daniel, Sabine Reuter, Christina H. Stuelten, Peng Li, Henry M. Sucov, Byung‐Gyu Kim, John J. Letterio, Karsten Kretschmer, Hye‐Jung Kim, Harald von Boehmer,

CAR-T cell therapy research

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.