論文 - 詳細
| RRC ID | 44674 |
|---|---|
| 著者 | Ogawa M, Okamura T, Ishikura S, Doi K, Matsuzaki H, Tanaka Y, Ota T, Hayakawa K, Suzuki H, Tsunoda T, Sasazuki T, Shirasawa S. |
| タイトル | Zfat-deficiency results in a loss of CD3ζ phosphorylation with dysregulation of ERK and Egr activities leading to impaired positive selection. |
| ジャーナル | PLoS One |
| Abstract |
The human ZFAT gene was originally identified as a susceptibility gene for autoimmune thyroid disease. Mouse Zfat is a critical transcriptional regulator for primitive hematopoiesis and required for peripheral T cell homeostasis. However, its physiological roles in T cell development remain poorly understood. Here, we generated Zfat (f/f)-LckCre mice and demonstrated that T cell-specific Zfat-deletion in Zfat (f/f)-LckCre mice resulted in a reduction in the number of CD4(+)CD8(+)double-positive (DP) cells, CD4(+)single positive cells and CD8(+)single positive cells. Indeed, in Zfat (f/f)-LckCre DP cells, positive selection was severely impaired. Defects of positive selection in Zfat-deficient thymocytes were not restored in the presence of the exogenous TCR by using TCR-transgenic mice. Furthermore, Zfat-deficient DP cells showed a loss of CD3ζ phosphorylation in response to T cell antigen receptor (TCR)-stimulation concomitant with dysregulation of extracellular signal-related kinase (ERK) and early growth response protein (Egr) activities. These results demonstrate that Zfat is required for proper regulation of the TCR-proximal signalings, and is a crucial molecule for positive selection through ERK and Egr activities, thus suggesting that a full understanding of the precise molecular mechanisms of Zfat will provide deeper insight into T cell development and immune regulation. |
| 巻・号 | 8(10) |
| ページ | e76254 |
| 公開日 | 2013-1-1 |
| DOI | 10.1371/journal.pone.0076254 |
| PII | PONE-D-13-19363 |
| PMID | 24098453 |
| PMC | PMC3789737 |
| MeSH | Animals CD3 Complex / metabolism* CD4-Positive T-Lymphocytes / cytology CD4-Positive T-Lymphocytes / metabolism CD8-Positive T-Lymphocytes / cytology CD8-Positive T-Lymphocytes / metabolism Cell Differentiation / immunology Clonal Selection, Antigen-Mediated / genetics* Clonal Selection, Antigen-Mediated / immunology* Early Growth Response Transcription Factors / genetics Early Growth Response Transcription Factors / metabolism* Extracellular Signal-Regulated MAP Kinases / metabolism* Gene Expression Regulation Immunophenotyping Male Mice Mice, Knockout Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / metabolism Phenotype Phosphorylation Receptors, Antigen, T-Cell / metabolism Thymocytes / cytology Thymocytes / metabolism Transcription Factors / deficiency* Transcription Factors / genetics Transcription Factors / metabolism |
| IF | 2.74 |
| 引用数 | 9 |
| WOS 分野 | IMMUNOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | TSt-4/G-DLL1(RCB2118) |