The Journal of Experimental Medicine
B-cell ELISpot from Mabtech
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 27 June 2005 doi:10.1084/jem.20050471
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 1, 33-45
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 3456K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Derbinski, J.
Right arrow Articles by Kyewski, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Derbinski, J.
Right arrow Articles by Kyewski, B.
Right arrowPubmed/NCBI databases
*GEO DataSet*GEO Profiles
*Substance via MeSH
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels

Jens Derbinski1, Jana Gäbler1, Benedikt Brors2, Sascha Tierling6, Sunitha Jonnakuty3, Manfred Hergenhahn4, Leena Peltonen5, Jörn Walter6, and Bruno Kyewski1

1 Division of Developmental Immunology, German Cancer Research Center, D-69120 Heidelberg, Germany
2 Division of Theoretical Bioinformatics, German Cancer Research Center, D-69120 Heidelberg, Germany
3 Division of Molecular Biophysics, German Cancer Research Center, D-69120 Heidelberg, Germany
4 Division of Genetic Alterations in Carcinogenesis, German Cancer Research Center, D-69120 Heidelberg, Germany
5 Department of Medical Genetics, University of Helsinki, 00029 HUS, Helsinki, Finland
6 Department of Genetics, Saarland University, D-66041 Saarbrücken, Germany

CORRESPONDENCE Bruno Kyewski: b.kyewski{at}dkfz.de

The role of central tolerance induction has recently been revised after the discovery of promiscuous expression of tissue-restricted self-antigens in the thymus. The extent of tissue representation afforded by this mechanism and its cellular and molecular regulation are barely defined. Here we show that medullary thymic epithelial cells (mTECs) are specialized to express a highly diverse set of genes representing essentially all tissues of the body. Most, but not all, of these genes are induced in functionally mature CD80hi mTECs. Although the autoimmune regulator (Aire) is responsible for inducing a large portion of this gene pool, numerous tissue-restricted genes are also up-regulated in mature mTECs in the absence of Aire. Promiscuously expressed genes tend to colocalize in clusters in the genome. Analysis of a particular gene locus revealed expression of clustered genes to be contiguous within such a cluster and to encompass both Aire-dependent and –independent genes. A role for epigenetic regulation is furthermore implied by the selective loss of imprinting of the insulin-like growth factor 2 gene in mTECs. Our data document a remarkable cellular and molecular specialization of the thymic stroma in order to mimic the transcriptome of multiple peripheral tissues and, thus, maximize the scope of central self-tolerance.

Abbreviations used: Aire, autoimmune regulator; ANOVA, analysis of variance; Cdkn1c, cyclin-dependent kinase inhibitor 1C; cTEC, cortical TEC; H19, H19 fetal liver mRNA; Igf2, insulin-like growth factor 2; LOI, loss of imprinting; mTEC, medullary TEC; SNuPE, single nucleotide primer extension; TEC, thymic epithelial cell; Tlbp; testis lipid binding protein; TRA, tissue-restricted antigen.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS