TGF-beta signalling contributes to thymic epithelial cell damage and regeneration following myeloablative conditioning and stem-cell transplantation

Hematopoietic stem cell transplantation (HSCT) is considered a potentially curative therapy for a number of severe autoimmune diseases. The rationale consists of deleting auto-reactive T and/or B cell clones and re-constructing a functional immune system tolerant to autoantigens. The re-emergence of T cell immunity following myeloablation largely depends on thymic de novo production of naïve T cells. The thymic stroma – mainly consisting of thymic epithelium (TE) – is responsible for the attraction of thymocyte precursor cells, support of developing T cells and appropriate positive and negative selection of a broad T cell receptor repertoire. Several reports including ours have demonstrated a negative impact of conditioning on TE numbers and function, which results in delayed T cell reconstitution. We have recently described the contribution of TGF-β signalling to thymic epithelial cell damage after irradiation, yet the underlying molecular mechanisms remain elusive.