2013年10月3日
Zfat-Deficiency Results in a Loss of CD3ζ Phosphorylation with Dysregulation of ERK and Egr Activities Leading to Impaired Positive Selection
PLoS ONE
- 巻
- 8
- 号
- 10
- 開始ページ
- e76254
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1371/journal.pone.0076254
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 Zfatf/f-LckCre mice and demonstrated that T cell-specific Zfat-deletion in Zfatf/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 Zfatf/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. © 2013 Ogawa et al.
- リンク情報
- ID情報
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- DOI : 10.1371/journal.pone.0076254
- ISSN : 1932-6203
- PubMed ID : 24098453
- SCOPUS ID : 84884849710