Cargando…
Cyp26b1 Regulates Retinoic Acid-Dependent Signals in T Cells and Its Expression Is Inhibited by Transforming Growth Factor-β
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 i...
Autores principales: | , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017564/ https://www.ncbi.nlm.nih.gov/pubmed/21249211 http://dx.doi.org/10.1371/journal.pone.0016089 |
_version_ | 1782195916584779776 |
---|---|
author | Takeuchi, Hajime Yokota, Aya Ohoka, Yoshiharu Iwata, Makoto |
author_facet | Takeuchi, Hajime Yokota, Aya Ohoka, Yoshiharu Iwata, Makoto |
author_sort | Takeuchi, Hajime |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-3017564 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30175642011-01-19 Cyp26b1 Regulates Retinoic Acid-Dependent Signals in T Cells and Its Expression Is Inhibited by Transforming Growth Factor-β Takeuchi, Hajime Yokota, Aya Ohoka, Yoshiharu Iwata, Makoto PLoS One Research Article 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. Public Library of Science 2011-01-07 /pmc/articles/PMC3017564/ /pubmed/21249211 http://dx.doi.org/10.1371/journal.pone.0016089 Text en Takeuchi et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Takeuchi, Hajime Yokota, Aya Ohoka, Yoshiharu Iwata, Makoto Cyp26b1 Regulates Retinoic Acid-Dependent Signals in T Cells and Its Expression Is Inhibited by Transforming Growth Factor-β |
title | Cyp26b1 Regulates Retinoic Acid-Dependent Signals in T Cells and Its Expression Is Inhibited by Transforming Growth Factor-β |
title_full | Cyp26b1 Regulates Retinoic Acid-Dependent Signals in T Cells and Its Expression Is Inhibited by Transforming Growth Factor-β |
title_fullStr | Cyp26b1 Regulates Retinoic Acid-Dependent Signals in T Cells and Its Expression Is Inhibited by Transforming Growth Factor-β |
title_full_unstemmed | Cyp26b1 Regulates Retinoic Acid-Dependent Signals in T Cells and Its Expression Is Inhibited by Transforming Growth Factor-β |
title_short | Cyp26b1 Regulates Retinoic Acid-Dependent Signals in T Cells and Its Expression Is Inhibited by Transforming Growth Factor-β |
title_sort | cyp26b1 regulates retinoic acid-dependent signals in t cells and its expression is inhibited by transforming growth factor-β |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017564/ https://www.ncbi.nlm.nih.gov/pubmed/21249211 http://dx.doi.org/10.1371/journal.pone.0016089 |
work_keys_str_mv | AT takeuchihajime cyp26b1regulatesretinoicaciddependentsignalsintcellsanditsexpressionisinhibitedbytransforminggrowthfactorb AT yokotaaya cyp26b1regulatesretinoicaciddependentsignalsintcellsanditsexpressionisinhibitedbytransforminggrowthfactorb AT ohokayoshiharu cyp26b1regulatesretinoicaciddependentsignalsintcellsanditsexpressionisinhibitedbytransforminggrowthfactorb AT iwatamakoto cyp26b1regulatesretinoicaciddependentsignalsintcellsanditsexpressionisinhibitedbytransforminggrowthfactorb |