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 gluco...
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Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_22111247_v26_n13_p3629_Taves http://hdl.handle.net/20.500.12110/paper_22111247_v26_n13_p3629_Taves |
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paper:paper_22111247_v26_n13_p3629_Taves2023-06-08T16:35:14Z Single-Cell Resolution and Quantitation of Targeted Glucocorticoid Delivery in the Thymus Cyp11b1 glucocorticoid receptor glucocorticoids lymphocytes nuclear receptors paracrine steroidogenesis steroids transcription factor 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. We use fluorescence detection of chromatin-associated GRs as biosensors of ligand binding and observe signals corresponding to steroid concentrations over physiological ranges in vitro and in vivo. In the thymus, where thymic epithelial cell (TEC)-synthesized glucocorticoids antagonize negative selection, we find that CD4 + CD8 + TCR hi cells, a small subset responding to self-antigens and undergoing selection, are specific targets of TEC-derived glucocorticoids and are exposed to 3-fold higher levels than other cells. These results demonstrate and quantitate targeted delivery of paracrine glucocorticoids. This approach may be used to assess in situ nuclear receptor signaling in a variety of physiological and pathological contexts. Glucocorticoids signal via the GR, a ligand-dependent transcription factor, and paracrine glucocorticoid signaling occurs in the thymus. Taves et al. use chromatin-associated GRs as biosensors to estimate glucocorticoid concentrations in vitro and in vivo. In the thymus, antigen-signaled CD4 + 8 + TCR hi cells are targeted by epithelial cell-synthesized glucocorticoids to promote positive selection. © 2019 2019 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_22111247_v26_n13_p3629_Taves http://hdl.handle.net/20.500.12110/paper_22111247_v26_n13_p3629_Taves |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
Cyp11b1 glucocorticoid receptor glucocorticoids lymphocytes nuclear receptors paracrine steroidogenesis steroids transcription factor |
spellingShingle |
Cyp11b1 glucocorticoid receptor glucocorticoids lymphocytes nuclear receptors paracrine steroidogenesis steroids transcription factor Single-Cell Resolution and Quantitation of Targeted Glucocorticoid Delivery in the Thymus |
topic_facet |
Cyp11b1 glucocorticoid receptor glucocorticoids lymphocytes nuclear receptors paracrine steroidogenesis steroids transcription factor |
description |
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. We use fluorescence detection of chromatin-associated GRs as biosensors of ligand binding and observe signals corresponding to steroid concentrations over physiological ranges in vitro and in vivo. In the thymus, where thymic epithelial cell (TEC)-synthesized glucocorticoids antagonize negative selection, we find that CD4 + CD8 + TCR hi cells, a small subset responding to self-antigens and undergoing selection, are specific targets of TEC-derived glucocorticoids and are exposed to 3-fold higher levels than other cells. These results demonstrate and quantitate targeted delivery of paracrine glucocorticoids. This approach may be used to assess in situ nuclear receptor signaling in a variety of physiological and pathological contexts. Glucocorticoids signal via the GR, a ligand-dependent transcription factor, and paracrine glucocorticoid signaling occurs in the thymus. Taves et al. use chromatin-associated GRs as biosensors to estimate glucocorticoid concentrations in vitro and in vivo. In the thymus, antigen-signaled CD4 + 8 + TCR hi cells are targeted by epithelial cell-synthesized glucocorticoids to promote positive selection. © 2019 |
title |
Single-Cell Resolution and Quantitation of Targeted Glucocorticoid Delivery in the Thymus |
title_short |
Single-Cell Resolution and Quantitation of Targeted Glucocorticoid Delivery in the Thymus |
title_full |
Single-Cell Resolution and Quantitation of Targeted Glucocorticoid Delivery in the Thymus |
title_fullStr |
Single-Cell Resolution and Quantitation of Targeted Glucocorticoid Delivery in the Thymus |
title_full_unstemmed |
Single-Cell Resolution and Quantitation of Targeted Glucocorticoid Delivery in the Thymus |
title_sort |
single-cell resolution and quantitation of targeted glucocorticoid delivery in the thymus |
publishDate |
2019 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_22111247_v26_n13_p3629_Taves http://hdl.handle.net/20.500.12110/paper_22111247_v26_n13_p3629_Taves |
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1768544433638211584 |