The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels
Open accessAbstract
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.
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Cites
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Self-citationParental imprinting of the mouse insulin-like growth factor II gene
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Cited by
Aschenbrenner, K., D'Cruz, L. M., Vollmann, E. H., Hinterberger, M., Emmerich, J., Swee, L. K., Rolink, A., & Klein, L. (2007) · Nature Immunology · doi:10.1038/ni1444 · Cited by 580
Osteoimmunology: The conceptual framework unifying the immune and skeletal systems
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Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance
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Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire
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Savage, P. A., Klawon, D. E. J., & Miller, C. H. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-100219-020937 · Cited by 321
Metadata
- Authors
- Derbinski, J., Gäbler, J., Brors, B., Tierling, S., Jonnakuty, S., Hergenhahn, M., Peltonen, L., Walter, J., & Kyewski, B.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2005-06-27
- Volume
- 202
- Issue
- 1
- Pages
- 33-45
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2160127445
- Cited by
- 553
- References
- 42
- FWCI
- 15.13
- Type
- journal article
- Language
- en
- Open access
- bronze
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