| First Author | Ferreirinha P | Year | 2021 |
| Journal | Eur J Immunol | Volume | 51 |
| Issue | 2 | Pages | 311-318 |
| PubMed ID | 32845012 | Mgi Jnum | J:302285 |
| Mgi Id | MGI:6506950 | Doi | 10.1002/eji.202048764 |
| Citation | Ferreirinha P, et al. (2021) A novel method to identify Post-Aire stages of medullary thymic epithelial cell differentiation. Eur J Immunol 51(2):311-318 |
| abstractText | Autoimmune regulator(+) (Aire) medullary thymic epithelial cells (mTECs) play a critical role in tolerance induction. Several studies demonstrated that Aire(+) mTECs differentiate further into Post-Aire cells. Yet, the identification of terminal stages of mTEC maturation depends on unique fate-mapping mouse models. Herein, we resolve this limitation by segmenting the mTEC(hi) (MHCII(hi) CD80(hi) ) compartment into mTEC(A/hi) (CD24(-) Sca1(-) ), mTEC(B/hi) (CD24(+) Sca1(-) ), and mTEC(C/hi) (CD24(+) Sca1(+) ). While mTEC(A/hi) included mostly Aire-expressing cells, mTEC(B/hi) contained Aire(+) and Aire(-) cells and mTEC(C/hi) were mainly composed of cells lacking Aire. The differential expression pattern of Aire led us to investigate the precursor-product relationship between these subsets. Strikingly, transcriptomic analysis of mTEC(A/hi) , mTEC(B/hi) , and mTEC(C/hi) sequentially mirrored the specific genetic program of Early-, Late- and Post-Aire mTECs. Corroborating their Post-Aire nature, mTEC(C/hi) downregulated the expression of tissue-restricted antigens, acquired traits of differentiated keratinocytes, and were absent in Aire-deficient mice. Collectively, our findings reveal a new and simple blueprint to survey late stages of mTEC differentiation. |
