Transforming Growth Factor-beta signaling in αβ thymocytes promotes negative selection.

In the thymus, the T lymphocyte repertoire is purged of a substantial portion of highly self-reactive cells. This negative selection process relies on the strength of TCR-signaling in response to self-peptide-MHC complexes, both in the cortex and medulla regions. However, whether cytokine-signaling contributes to negative selection remains unclear.

Administration of RANKL boosts thymic regeneration upon bone marrow transplantation.

Cytoablative treatments lead to severe damages on thymic epithelial cells (TECs), which result in delayed thymopoiesis and a prolonged period of T-cell immunodeficiency. Understanding the mechanisms that govern thymic regeneration is of paramount interest for the recovery of a functional immune system notably after bone marrow transplantation (BMT). Here, we show that RANK ligand (RANKL) is upregulated in CD4 thymocytes and lymphoid tissue inducer (LTi) cells during the early phase of thymic regeneration.