| 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
|
| リソース情報 |
| ヒト・動物細胞 |
TSt-4/G-DLL1(RCB2118) |
