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Publication : Lineage tracing and cell ablation identify a post-Aire-expressing thymic epithelial cell population.

First Author  Metzger TC Year  2013
Journal  Cell Rep Volume  5
Issue  1 Pages  166-79
PubMed ID  24095736 Mgi Jnum  J:203553
Mgi Id  MGI:5527342 Doi  10.1016/j.celrep.2013.08.038
Citation  Metzger TC, et al. (2013) Lineage tracing and cell ablation identify a post-Aire-expressing thymic epithelial cell population. Cell Rep 5(1):166-79
abstractText  Thymic epithelial cells in the medulla (mTECs) play a critical role in enforcing central tolerance through expression and presentation of tissue-specific antigens (TSAs) and deletion of autoreactive thymocytes. TSA expression requires autoimmune regulator (Aire), a transcriptional activator present in a subset of mTECs characterized by high CD80 and major histocompatibility complex II expression and a lack of potential for differentiation or proliferation. Here, using an Aire-DTR transgenic line, we show that short-term ablation specifically targets Aire(+) mTECs, which quickly undergo RANK-dependent recovery. Repeated ablation also affects Aire(-) mTECs, and using an inducible Aire-Cre fate-mapping system, we find that this results from the loss of a subset of mTECs that showed prior expression of Aire, maintains intermediate TSA expression, and preferentially migrates toward the center of the medulla. These results clearly identify a distinct stage of mTEC development and underscore the diversity of mTECs that play a key role in maintaining tolerance.
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