[PDF][PDF] Lineage tracing and cell ablation identify a post-Aire-expressing thymic epithelial cell population

TC Metzger, IS Khan, JM Gardner, ML Mouchess… - Cell reports, 2013 - cell.com
TC Metzger, IS Khan, JM Gardner, ML Mouchess, KP Johannes, AK Krawisz…
Cell reports, 2013cell.com
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 …
Summary
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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