Document Detail

Mesenchymal cells regulate retinoic acid receptor-dependent cortical thymic epithelial cell homeostasis.
MedLine Citation:
PMID:  22504647     Owner:  NLM     Status:  MEDLINE    
The vitamin A metabolite and transcriptional modulator retinoic acid (RA) is recognized as an important regulator of epithelial cell homeostasis in several tissues. Despite the known importance of the epithelial compartment of the thymus in T cell development and selection, the potential role of RA in the regulation of thymic cortical and medullary epithelial cell homeostasis has yet to be addressed. In this study, using fetal thymus organ cultures, we demonstrate that endogenous RA signaling promotes thymic epithelial cell (TEC) cell-cycle exit and restricts TEC cellularity preferentially in the cortical TEC compartment. Combined gene expression, biochemical, and functional analyses identified mesenchymal cells as the major source of RA in the embryonic thymus. In reaggregate culture experiments, thymic mesenchyme was required for RA-dependent regulation of TEC expansion, highlighting the importance of mesenchyme-derived RA in modulating TEC turnover. The RA-generating potential of mesenchymal cells was selectively maintained within a discrete Ly51(int)gp38(+) subset of Ly51(+) mesenchyme in the adult thymus, suggesting a continual role for mesenchymal cell-derived RA in postnatal TEC homeostasis. These findings identify RA signaling as a novel mechanism by which thymic mesenchyme influences TEC development.
Katarzyna M Sitnik; Knut Kotarsky; Andrea J White; William E Jenkinson; Graham Anderson; William W Agace
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-13
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  188     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-04     Completed Date:  2012-08-07     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4801-9     Citation Subset:  AIM; IM    
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MeSH Terms
Cell Cycle / immunology
Epithelial Cells / immunology*
Homeostasis / immunology*
Mesenchymal Stromal Cells / immunology*,  metabolism*
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Organ Culture Techniques
Receptors, Retinoic Acid / physiology*
Signal Transduction / immunology,  physiology
T-Lymphocyte Subsets / cytology,  immunology,  metabolism
Thymus Gland / cytology*,  embryology,  immunology*
Grant Support
G0401620//Medical Research Council; G1000213//Medical Research Council; G1001055//Medical Research Council
Reg. No./Substance:
0/Receptors, Retinoic Acid

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

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