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The Journal of Experimental Medicine

Year: 2009  |  Volume: 206  |  Issue: 10  |  Page No.: 2131 - 2139

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

J Nolting, C Daniel, S Reuter, C Stuelten, P Li, H Sucov, B. G Kim, J. J Letterio, K Kretschmer, H. J Kim and H. von Boehmer

Abstract

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 (RAR) but did not require Smad3, despite the fact that RA enhanced Smad3 expression. The RAR1 isoform was not essential for RA-dependent enhancement of transforming growth factor β–driven conversion, suggesting that conversion can also be mediated by RAR2. Interleukin (IL)-6 strongly reduced RAR expression levels such that a deficiency of the predominant RAR1 isoform leaves too little RAR2 for RA to inhibit the generation of Th17 cells in the presence of IL-6.

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