| First Author | Giampaolo S | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 3 | Pages | 106234 |
| PubMed ID | 36926655 | Mgi Jnum | J:334082 |
| Mgi Id | MGI:7446052 | Doi | 10.1016/j.isci.2023.106234 |
| Citation | Giampaolo S, et al. (2023) NFATc1 induction by an intronic enhancer restricts NKT gammadelta cell formation. iScience 26(3):106234 |
| abstractText | In thymus, the ablation of T cell receptor (TCR)-activated transcription factor NFATc1 or its inducible isoforms during the double-negative (DN) stages of thymocyte development leads to a marked increase in gammadelta thymocytes whereas the development of alphabeta thymocytes remains mostly unaffected. These gammadelta thymocytes are characterized by the upregulation of the promyelocytic leukemia zinc-finger factor (PLZF), the "master regulator" of natural killer T (NKT) cell development, and the acquisition of an NKT gammadelta cell phenotype with higher cell survival rates. The suppressive function of NFATc1 in NKT gammadelta cell formation critically depends on the remote enhancer E2, which is essential for the inducible expression of NFATc1 directed by its distal promoter P1. Thus, the enhancer deciphers a strong gammadelta TCR signal into the expression of inducible NFATc1 isoforms resulting in high levels of NFATc1 protein that are essential to control the numbers of NKT gammadelta cells. |
