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

Cell Rep. 2013 Oct 17;5(1):166-79. doi: 10.1016/j.celrep.2013.08.038. Epub 2013 Oct 3.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism*
  • Female
  • Humans
  • Mice
  • Mice, Transgenic
  • Signal Transduction
  • Thymocytes / cytology*
  • Thymocytes / metabolism*
  • Thymus Gland / cytology*
  • Thymus Gland / metabolism*