Fig. 5: Effects of steroids on T lymphocytes.
A Sex steroids decrease the expression of Dll in cortical thymic epithelial cells (cTEC), which results increase thymopoiesis. Dihydrotestosterone (DHT) increases the expression of AIRE in medullary thymic epithelial cells and assists in negative selection of T cells, on the other hand estrogens exhibit opposite effect by decreasing AIRE transcription. CD11c+ cortical dendritic cells play a crucial role in clonal deletion of activated caspase. B In presence of steroids DCs fail to prime T helper cells toward Th1. C CD28 signaling protects single positive T cells from glucocorticoid-induced apoptosis. This event exclusively occurs in later stage of thymocyte maturation. B7-1 (CD80) and B7-2 (CD86) are the ligands of CD28 are expressed in the corticomedullary region and medullary region of thymus where only single positive T cells are observed. CD28 signaling is crucial to maintain sustained expression of antiapoptotic molecule Bcl-XL and downregulate the expression of pro-apoptotic molecule Bak via calmodulin and phosphatidylinositol 3 kinase (PI3K)-dependent pathway D Glucocorticoid-bound glucocorticoids receptor (GC/GR) induces glucocorticoid-induced leucine zipper (GILZ), which in turn induce FoxP3 expression, and thereby promoted peripheral Treg (pTreg) differentiation. (Figure created with BioRender.com).
