| Formation of a functional thymus initiated by a postnatal epithelial progenitor cell. | |
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MedLine Citation:
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PMID: 16791198 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The thymus is essential for the generation of self-tolerant effector and regulatory T cells. Intrathymic T-cell development requires an intact stromal microenvironment, of which thymic epithelial cells (TECs) constitute a major part. For instance, cell-autonomous genetic defects of forkhead box N1 (Foxn1) and autoimmune regulator (Aire) in thymic epithelial cells cause primary immunodeficiency and autoimmunity, respectively. During development, the thymic epithelial rudiment gives rise to two major compartments, the cortex and medulla. Cortical TECs positively select T cells, whereas medullary TECs are involved in negative selection of potentially autoreactive T cells. It has long been unclear whether these two morphologically and functionally distinct types of epithelial cells arise from a common bi-potent progenitor cell and whether such progenitors are still present in the postnatal period. Here, using in vivo cell lineage analysis in mice, we demonstrate the presence of a common progenitor of cortical and medullary TECs after birth. To probe the function of postnatal progenitors, a conditional mutant allele of Foxn1 was reverted to wild-type function in single epithelial cells in vivo. This led to the formation of small thymic lobules containing both cortical and medullary areas that supported normal thymopoiesis. Thus, single epithelial progenitor cells can give rise to a complete and functional thymic microenvironment, suggesting that cell-based therapies could be developed for thymus disorders. |
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Authors:
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Conrad C Bleul; Tatiana Corbeaux; Alexander Reuter; Paul Fisch; Jürgen Schulte Mönting; Thomas Boehm |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Nature Volume: 441 ISSN: 1476-4687 ISO Abbreviation: Nature Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2006-06-22 Completed Date: 2006-07-12 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0410462 Medline TA: Nature Country: England |
Other Details:
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Languages: eng Pagination: 992-6 Citation Subset: IM |
Affiliation:
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Department of Developmental Immunology, Max-Planck Institute of Immunobiology, Stuebeweg 51, D-79108 Freiburg, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Lineage* Epithelial Cells / cytology, metabolism Forkhead Transcription Factors / biosynthesis, genetics Humans Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Nude Mice, Transgenic Stem Cells / cytology*, metabolism T-Lymphocytes / metabolism Thymus Gland / cytology*, growth & development, immunology |
| Chemical | |
Reg. No./Substance:
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0/Forkhead Transcription Factors; 0/Whn protein |
| Comments/Corrections | |
Comment In:
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Nature. 2006 Jun 22;441(7096):942-3
[PMID:
16791184
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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