RelB intrinsically regulates the development and function of medullary thymic epithelial cells.

Medullary thymic epithelial cells (mTECs) act as one of the major stromal components in the thymus for selection and maturation of both conventional T cells and non-conventional T cells. Extensive efforts have been spent to understand how mTEC development and function are regulated. Although RelB has been well accepted to be a critical transcriptional factor for mTEC development, the underlying mechanisms still remain largely unclear. In this study, by generating thymic epithelial cell specific RelB deficient mice, we found that epithelial intrinsic RelB is required for mTEC homeostatic proliferation. Mechanistically, RelB regulates the expression of genes involved in cell cycle. Functionally, lack of intrinsic RelB in thymic epithelial cells results in dramatically reduced population of mTECs and impaired development of thymic invariant natural killer T (iNKT) cells and intraepithelial lymphocyte precursors (IELPs). This study thus reveals an epithelial intrinsic role of RelB on mTEC development and function.