Document Detail


Formation of a functional thymus initiated by a postnatal epithelial progenitor cell.
MedLine Citation:
PMID:  16791198     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Conrad C Bleul; Tatiana Corbeaux; Alexander Reuter; Paul Fisch; Jürgen Schulte Mönting; Thomas Boehm
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature     Volume:  441     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-22     Completed Date:  2006-07-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  992-6     Citation Subset:  IM    
Affiliation:
Department of Developmental Immunology, Max-Planck Institute of Immunobiology, Stuebeweg 51, D-79108 Freiburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
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:
0/Forkhead Transcription Factors; 0/Whn protein
Comments/Corrections
Comment In:
Nature. 2006 Jun 22;441(7096):942-3   [PMID:  16791184 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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