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

Abstract

Thymic epithelial cells (TEC) control T cell development and play essential roles in establishing self-tolerance. By using <i>Foxn1-Cre</i>-driven ablation of <i>Klf6</i> gene in TEC, we identified <i>Klf6</i> as a critical factor in TEC development. <i>Klf6</i> 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. <i>Klf6</i> 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.