| First Author | Akiyama N | Year | 2016 |
| Journal | J Exp Med | Volume | 213 |
| Issue | 8 | Pages | 1441-58 |
| PubMed ID | 27401343 | Mgi Jnum | J:236470 |
| Mgi Id | MGI:5806181 | Doi | 10.1084/jem.20151780 |
| Citation | Akiyama N, et al. (2016) Identification of embryonic precursor cells that differentiate into thymic epithelial cells expressing autoimmune regulator. J Exp Med 213(8):1441-58 |
| abstractText | Medullary thymic epithelial cells (mTECs) expressing autoimmune regulator (Aire) are critical for preventing the onset of autoimmunity. However, the differentiation program of Aire-expressing mTECs (Aire(+) mTECs) is unclear. Here, we describe novel embryonic precursors of Aire(+) mTECs. We found the candidate precursors of Aire(+) mTECs (pMECs) by monitoring the expression of receptor activator of nuclear factor-kappaB (RANK), which is required for Aire(+) mTEC differentiation. pMECs unexpectedly expressed cortical TEC molecules in addition to the mTEC markers UEA-1 ligand and RANK and differentiated into mTECs in reaggregation thymic organ culture. Introduction of pMECs in the embryonic thymus permitted long-term maintenance of Aire(+) mTECs and efficiently suppressed the onset of autoimmunity induced by Aire(+) mTEC deficiency. Mechanistically, pMECs differentiated into Aire(+) mTECs by tumor necrosis factor receptor-associated factor 6-dependent RANK signaling. Moreover, nonclassical nuclear factor-kappaB activation triggered by RANK and lymphotoxin-beta receptor signaling promoted pMEC induction from progenitors exhibiting lower RANK expression and higher CD24 expression. Thus, our findings identified two novel stages in the differentiation program of Aire(+) mTECs. |
