التفاصيل البيبلوغرافية
| العنوان: |
Cyp26b1 Regulates Retinoic Acid-Dependent Signals in T Cells and Its Expression Is Inhibited by Transforming Growth Factor-β. |
| المؤلفون: |
Takeuchi, Hajime1,2 takeuchih@kph.bunri-u.ac.jp, Yokota, Aya1,2, Ohoka, Yoshiharu1,2, Iwata, Makoto1,2 iwatam@kph.bunri-u.ac.jp |
| المصدر: |
PLoS ONE. 2011, Vol. 6 Issue 1, p1-8. 8p. |
| مصطلحات موضوعية: |
*VITAMIN A, *METABOLITES, *TRETINOIN, *LYMPHOCYTES, *DENDRITIC cells, *T cells, *TRANSFORMING growth factors, *ANTIGENS, *MEDICAL research |
| مستخلص: |
Background: The vitamin A metabolite, retinoic acid (RA), plays important roles in the regulation of lymphocyte properties. Dendritic cells in gut-related lymphoid organs can produce RA, thereby imprinting gut-homing specificity on T cells and enhancing transforming growth factor (TGF)-β-dependent induction of Foxp3+ regulatory T cells upon antigen presentation. In general, RA concentrations in cells and tissues are regulated by its degradation as well. However, it remained unclear if T cells could actively catabolize RA. Methodology/Principal Findings: We assessed the expression of known RA-catabolizing enzymes in T cells from mouse lymphoid tissues. Antigen-experienced CD44+ T cells in gut-related lymphoid organs selectively expressed Cyp26b1, a member of the cytochrome P450 family 26. However, T cells in the spleen or skin-draining lymph nodes did not significantly express Cyp26b1. Accordingly, physiological levels of RA (1-10 nM) could induce Cyp26b1 expression in naïve T cells upon activation in vitro, but could not do so in the presence of TGF-β. Overexpression of Cyp26b1 significantly suppressed the RA effect to induce expression of the gut-homing receptor CCR9 on T cells. On the other hand, knocking down Cyp26b1 gene expression with small interfering RNA or inhibiting CYP26 enzymatic activity led to enhancement of the RA-induced CCR9 expression. Conclusions/Significance: Our data demonstrate a role for CYP26B1 in regulating RA-dependent signals in activated T cells but not during TGF-β-dependent differentiation to Foxp3+ regulatory T cells. Aberrant expression of CYP26B1 may disturb T cell trafficking and differentiation in the gut and its related lymphoid organs. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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