Expression of the transcription factor Klf6 by thymic epithelial cells is required for thymus development

• Published in: Science advances 2023-11, Vol.9 (46), p.eadg8126-eadg8126
• Main Authors: Malin, Justin, Martinez-Ruiz, Gustavo Ulises, Zhao, Yongge, Shissler, Susannah C, Cowan, Jennifer E, Ding, Yi, Morales-Sanchez, Abigail, Ishikawa, Masaki, Lavaert, Marieke, Das, Arundhoti, Butcher, Donna, Warner, Andrew C, Kallarakal, Melissa, Chen, Jingqiu, Kedei, Noemi, Kelly, Michael, Brinster, Lauren R, Allman, David, Bhandoola, Avinash
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - genetics; Chromatin - metabolism; Epithelial Cells - metabolism; Gene Expression Regulation; Mice; Mice, Inbred C57BL; Thymocytes - metabolism; Thymus Gland - metabolism
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.adg8126

Thymic epithelial cells (TEC) control T cell development and play essential roles in establishing self-tolerance. By using -driven ablation of gene in TEC, we identified as a critical factor in TEC development. 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. deficiency altered chromatin accessibility and affected TEC chromatin configuration. Consistent with these defects, naïve 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.