| First Author | Malin J | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 46 | Pages | eadg8126 |
| PubMed ID | 37967174 | Mgi Jnum | J:342615 |
| Mgi Id | MGI:7550069 | Doi | 10.1126/sciadv.adg8126 |
| Citation | Malin J, et al. (2023) Expression of the transcription factor Klf6 by thymic epithelial cells is required for thymus development. Sci Adv 9(46):eadg8126 |
| abstractText | Thymic epithelial cells (TEC) control T cell development and play essential roles in establishing self-tolerance. By using Foxn1-Cre-driven ablation of Klf6 gene in TEC, we identified Klf6 as a critical factor in TEC development. Klf6 deficiency resulted in a hypoplastic thymus-evident from fetal stages into adulthood-in which a dramatic increase in the frequency of apoptotic TEC was observed. Among cortical TEC (cTEC), a previously unreported cTEC population expressing the transcription factor Sox10 was relatively expanded. Within medullary TEC (mTEC), mTEC I and Tuft-like mTEC IV were disproportionately decreased. Klf6 deficiency altered chromatin accessibility and affected TEC chromatin configuration. Consistent with these defects, naive conventional T cells and invariant natural killer T cells were reduced in the spleen. Late stages of T cell receptor-dependent selection of thymocytes were affected, and mice exhibited autoimmunity. Thus, Klf6 has a prosurvival role and affects the development of specific TEC subsets contributing to thymic function. |
