MISC

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
  • Masahiro Ogawa
  • Tadashi Okamura
  • Shuhei Ishikura
  • Keiko Doi
  • Hiroshi Matsuzaki
  • Yoko Tanaka
  • Takeharu Ota
  • Kunihiro Hayakawa
  • Harumi Suzuki
  • Toshiyuki Tsunoda
  • Takehiko Sasazuki
  • Senji Shirasawa
  • 全て表示

8
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
DOI
https://doi.org/10.1371/journal.pone.0076254
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/24098453
ID情報
  • DOI : 10.1371/journal.pone.0076254
  • ISSN : 1932-6203
  • PubMed ID : 24098453
  • SCOPUS ID : 84884849710

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