Glucocorticoids Oppose Thymocyte Negative Selection by Inhibiting Helios and Nur77.

ABSTRACT: Glucocorticoid (GC) signaling in thymocytes shapes the TCR repertoire by antagonizing thymocyte negative selection. The transcription factors Nur77 and Helios, which are upregulated in TCR-signaled thymocytes, have been implicated in negative selection. In this study, we found that GCs inhibited Helios and, to a lesser extent, Nur77 upregulation in TCR-stimulated mouse thymocytes. Inhibition was increased by GC preincubation, and reductions in mRNA were prevented by a protein synthesis inhibitor, suggesting that GCs suppress indirectly via an intermediary factor. Upregulation of Helios in TCR-stimulated thymocytes was unaffected by deletion of Nur77, indicating Nur77 and Helios are regulated independently. Whereas CD4⁺ thymocytes are positively selected in wild-type AND TCR-tran

SUBMITTER: Mittelstadt PR 

PROVIDER: S-EPMC6783372 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature