| RRC ID |
28598
|
| 著者 |
Ohoka Y, Yokota A, Takeuchi H, Maeda N, Iwata M.
|
| タイトル |
Retinoic acid-induced CCR9 expression requires transient TCR stimulation and cooperativity between NFATc2 and the retinoic acid receptor/retinoid X receptor complex.
|
| ジャーナル |
J Immunol
|
| Abstract |
Retinoic acid (RA) imprints gut-homing specificity on T cells upon activation by inducing the expression of chemokine receptor CCR9 and integrin α4β7. CCR9 expression seemed to be more highly dependent on RA than was the α4β7 expression, but its molecular mechanism remained unclear. In this article, we show that NFAT isoforms NFATc1 and NFATc2 directly interact with RA receptor (RAR) and retinoid X receptor (RXR) but play differential roles in RA-induced CCR9 expression on murine naive CD4(+) T cells. TCR stimulation for 6-24 h was required for the acquisition of responsiveness to RA and induced activation of NFATc1 and NFATc2. However, RA failed to induce CCR9 expression as long as TCR stimulation continued. After terminating TCR stimulation or adding cyclosporin A to the culture, Ccr9 gene transcription was induced, accompanied by inactivation of NFATc1 and sustained activation of NFATc2. Reporter and DNA-affinity precipitation assays demonstrated that the binding of NFATc2 to two NFAT-binding sites and that of the RAR/RXR complex to an RA response element half-site in the 5'-flanking region of the mouse Ccr9 gene were critical for RA-induced promoter activity. NFATc2 directly bound to RARα and RXRα, and it enhanced the binding of RARα to the RA response element half-site. NFATc1 also bound to the NFAT-binding sites and directly to RARα and RXRα, but it inhibited the NFATc2-dependent promoter activity. These results suggest that the cooperativity between NFATc2 and the RAR/RXR complex is essential for CCR9 expression on T cells and that NFATc1 interferes with the action of NFATc2.
|
| 巻・号 |
186(2)
|
| ページ |
733-44
|
| 公開日 |
2011-1-15
|
| DOI |
10.4049/jimmunol.1000913
|
| PII |
jimmunol.1000913
|
| PMID |
21148038
|
| MeSH |
Animals
Base Sequence
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / metabolism
COS Cells
Cell Line, Tumor
Cells, Cultured
Chlorocebus aethiops
Coculture Techniques
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Molecular Sequence Data
NFATC Transcription Factors / antagonists & inhibitors
NFATC Transcription Factors / metabolism
NFATC Transcription Factors / physiology*
Promoter Regions, Genetic / immunology
Protein Binding / immunology
Receptors, Antigen, T-Cell / deficiency
Receptors, Antigen, T-Cell / genetics
Receptors, Antigen, T-Cell / physiology*
Receptors, CCR / biosynthesis*
Receptors, Retinoic Acid / physiology*
Retinoid X Receptors / physiology*
Time Factors
Tretinoin / pharmacology*
|
| IF |
4.886
|
| 引用数 |
38
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| 遺伝子材料 |
pGL3-CCR9pro (RDB08511) |
