| T Cell Factor 1 Regulates Thymocyte Survival via a RORγt-Dependent Pathway. | |
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MedLine Citation:
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PMID: 22039299 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Survival of CD4(+)CD8(+) double-positive (DP) thymocytes plays a critical role in shaping the peripheral T cell repertoire. However, the mechanisms responsible for the regulation of DP thymocyte lifespan remain poorly understood. In this work, we demonstrate that T cell factor (TCF)-1 regulates DP thymocyte survival by upregulating RORγt. Microarray analysis revealed that RORγt was significantly downregulated in TCF-1(-/-) thymocytes that underwent accelerated apoptosis, whereas RORγt was greatly upregulated in thymocytes that had enhanced survival due to transgenic expression of a stabilized β-catenin (β-cat(Tg)), a TCF-1 activator. Both TCF-1(-/-) and RORγt(-/-) DP thymocytes underwent similar accelerated apoptosis. Forced expression of RORγt successfully rescued TCF-1(-/-) DP thymocytes from apoptosis, whereas ectopically expressed TCF-1 was not able to rescue the defective T cell development because of the lack of RORγt-supported survival. Furthermore, activation of TCF-1 by stabilized β-catenin was able to enhance DP thymocyte survival only in the presence of RORγt, indicating that RORγt acts downstream of TCF-1 in the regulation of DP thymocyte survival. Moreover, β-catenin/TCF-1 directly interacted with the RORγt promoter region and stimulated its activity. Therefore, our data demonstrated that TCF-1 enhances DP thymocyte survival through transcriptional upregulation of RORγt, which we previously showed is an essential prosurvival molecule for DP thymocytes. |
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Authors:
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Ruiqing Wang; Huimin Xie; Zhaofeng Huang; Jian Ma; Xianfeng Fang; Yan Ding; Zuoming Sun |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-28 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: - ISSN: 1550-6606 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-31 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Immunology, Beckman Research Institute, City of Hope, Duarte, CA 91010; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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