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• W1504329203 endingPage "2861" @default.
• W1504329203 startingPage "2851" @default.
• W1504329203 abstract "Abstract Vitamin A is established as an important immune regulator, but the mechanisms whereby vitamin A regulates T cell biology are poorly defined. In this study, we show that an active metabolite of vitamin A, all-trans retinoic acid (RA), potently stimulates T cell proliferation by modulating IL-2-mediated signaling downstream of IL-2R and independent of the induction of IL-2. Thus, at concentrations as low as 0.1 nM, RA enhanced the division of normal human T lymphocytes that were simultaneously stimulated with anti-CD3 mAbs and saturating concentrations of IL-2. At the optimal concentration of RA (50 nM), a 3-fold increase in T cell proliferation was observed. The induced proliferation was preceded by increased phosphorylation of the retinoblastoma protein and enhanced G1- to S-phase progression. Interestingly, the promitogenic effect of RA was found to be particularly directed toward increased expression of cyclin D3 at both the mRNA and protein level. Furthermore, the stimulatory effect of RA on cyclin D3 expression as well as on cell proliferation was completely abolished in the presence of the JAK inhibitor AG-490 or blocking IL-2Rα mAbs, and RA also enhanced cyclin D3 expression and T cell proliferation in the presence of IL-2 alone. Finally, we showed that the proliferative effect of RA was mimicked by agonists of the retinoic acid receptor (RAR) and completely inhibited by a RAR-selective antagonist. In conclusion, our results indicate that RA, via RAR, stimulates IL-2-induced signaling in a JAK-dependent manner to enhance cyclin D3 expression and thereby promote T cell proliferation." @default.
• W1504329203 created "2016-06-24" @default.
• W1504329203 creator A5059762173 @default.
• W1504329203 creator A5062057544 @default.
• W1504329203 creator A5084860151 @default.
• W1504329203 creator A5086983040 @default.
• W1504329203 date "2006-09-01" @default.
• W1504329203 modified "2023-10-18" @default.
• W1504329203 title "All-<i>trans</i>Retinoic Acid Stimulates IL-2-Mediated Proliferation of Human T Lymphocytes: Early Induction of Cyclin D3" @default.
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• W1504329203 doi "https://doi.org/10.4049/jimmunol.177.5.2851" @default.
• W1504329203 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16920920" @default.
• W1504329203 hasPublicationYear "2006" @default.
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