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Intestinal Epithelial Cells Synthesize Glucocorticoids and Regulate T Cell Activation

Glucocorticoids (GCs) are important steroid hormones with widespread activities in metabolism, development, and immune regulation. The adrenal glands are the major source of GCs and release these hormones in response to psychological and immunological stress. However, there is increasing evidence th...

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Autores principales: Cima, Igor, Corazza, Nadia, Dick, Bernhard, Fuhrer, Andrea, Herren, Simon, Jakob, Sabine, Ayuni, Erick, Mueller, Christoph, Brunner, Thomas
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211994/
https://www.ncbi.nlm.nih.gov/pubmed/15596520
http://dx.doi.org/10.1084/jem.20031958
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author Cima, Igor
Corazza, Nadia
Dick, Bernhard
Fuhrer, Andrea
Herren, Simon
Jakob, Sabine
Ayuni, Erick
Mueller, Christoph
Brunner, Thomas
author_facet Cima, Igor
Corazza, Nadia
Dick, Bernhard
Fuhrer, Andrea
Herren, Simon
Jakob, Sabine
Ayuni, Erick
Mueller, Christoph
Brunner, Thomas
author_sort Cima, Igor
collection PubMed
description Glucocorticoids (GCs) are important steroid hormones with widespread activities in metabolism, development, and immune regulation. The adrenal glands are the major source of GCs and release these hormones in response to psychological and immunological stress. However, there is increasing evidence that GCs may also be synthesized by nonadrenal tissues. Here, we report that the intestinal mucosa expresses steroidogenic enzymes and releases the GC corticosterone in response to T cell activation. T cell activation causes an increase in the intestinal expression of the steroidogenic enzymes required for GC synthesis. In situ hybridization analysis revealed that these enzymes are confined to the crypt region of the intestinal epithelial layer. Surprisingly, in situ–produced GCs exhibit both an inhibitory and a costimulatory role on intestinal T cell activation. In the absence of intestinal GCs in vivo, activation by anti-CD3 injection resulted in reduced CD69 expression and interferon-γ production by intestinal T cells, whereas activation by viral infection led to increased T cell activation. We conclude that the intestinal mucosa is a potent source of immunoregulatory GCs.
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spelling pubmed-22119942008-03-11 Intestinal Epithelial Cells Synthesize Glucocorticoids and Regulate T Cell Activation Cima, Igor Corazza, Nadia Dick, Bernhard Fuhrer, Andrea Herren, Simon Jakob, Sabine Ayuni, Erick Mueller, Christoph Brunner, Thomas J Exp Med Article Glucocorticoids (GCs) are important steroid hormones with widespread activities in metabolism, development, and immune regulation. The adrenal glands are the major source of GCs and release these hormones in response to psychological and immunological stress. However, there is increasing evidence that GCs may also be synthesized by nonadrenal tissues. Here, we report that the intestinal mucosa expresses steroidogenic enzymes and releases the GC corticosterone in response to T cell activation. T cell activation causes an increase in the intestinal expression of the steroidogenic enzymes required for GC synthesis. In situ hybridization analysis revealed that these enzymes are confined to the crypt region of the intestinal epithelial layer. Surprisingly, in situ–produced GCs exhibit both an inhibitory and a costimulatory role on intestinal T cell activation. In the absence of intestinal GCs in vivo, activation by anti-CD3 injection resulted in reduced CD69 expression and interferon-γ production by intestinal T cells, whereas activation by viral infection led to increased T cell activation. We conclude that the intestinal mucosa is a potent source of immunoregulatory GCs. The Rockefeller University Press 2004-12-20 /pmc/articles/PMC2211994/ /pubmed/15596520 http://dx.doi.org/10.1084/jem.20031958 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Cima, Igor
Corazza, Nadia
Dick, Bernhard
Fuhrer, Andrea
Herren, Simon
Jakob, Sabine
Ayuni, Erick
Mueller, Christoph
Brunner, Thomas
Intestinal Epithelial Cells Synthesize Glucocorticoids and Regulate T Cell Activation
title Intestinal Epithelial Cells Synthesize Glucocorticoids and Regulate T Cell Activation
title_full Intestinal Epithelial Cells Synthesize Glucocorticoids and Regulate T Cell Activation
title_fullStr Intestinal Epithelial Cells Synthesize Glucocorticoids and Regulate T Cell Activation
title_full_unstemmed Intestinal Epithelial Cells Synthesize Glucocorticoids and Regulate T Cell Activation
title_short Intestinal Epithelial Cells Synthesize Glucocorticoids and Regulate T Cell Activation
title_sort intestinal epithelial cells synthesize glucocorticoids and regulate t cell activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211994/
https://www.ncbi.nlm.nih.gov/pubmed/15596520
http://dx.doi.org/10.1084/jem.20031958
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