Glucocorticoids Oppose Thymocyte Negative Selection by Inhibiting Helios and Nur77.

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.

Single-Cell Resolution and Quantitation of Targeted Glucocorticoid Delivery in the Thymus.

Glucocorticoids are lipid-soluble hormones that signal via the glucocorticoid receptor (GR), a ligand-dependent transcription factor. Circulating glucocorticoids derive from the adrenals, but it is now apparent that paracrine glucocorticoid signaling occurs in multiple tissues. Effective local glucocorticoid concentrations and whether glucocorticoid delivery can be targeted to specific cell subsets are unknown.

Cutting Edge: De Novo Glucocorticoid Synthesis by Thymic Epithelial Cells Regulates Antigen-Specific Thymocyte Selection.

Glucocorticoid (GC) signaling in thymocytes counters negative selection and promotes the generation of a self-tolerant yet Ag-responsive T cell repertoire. Whereas circulating GC are derived from the adrenals, GC are also synthesized de novo in the thymus. The significance of this local production is unknown.

Intensity and duration of TCR signaling is limited by p38 phosphorylation of ZAP-70 and destabilization of the signalosome.

ZAP-70 is a tyrosine kinase that is essential for initiation of T cell antigen receptor (TCR) signaling. We have found that T cell p38 MAP kinase (MAPK), which is directly phosphorylated and activated by ZAP-70 downstream of the TCR, in turn phosphorylates Thr-293 in the interdomain B region of ZAP-70. Mutant T cells expressing ZAP-70 with an alanine substitution at this residue (ZAP-70) had enhanced TCR proximal signaling and increased effector responses.

Parallel dual-task processing and task-shielding in older and younger adults: Behavioral and diffusion model results.

Unlabelled: Background/Study Context: The study investigated the Backward Crosstalk Effect (BCE) in dual-task situations, that is, the observation that Task 2 characteristics can even influence Task 1 processing. This observation suggests that the tasks are processed in parallel. Besides determining the existence of a BCE in a group of older adults, the size of the BCE was compared to that in a group of younger adults.