Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1782148600009064448 |
---|---|
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. |
format | Text |
id | pubmed-2211994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT cimaigor intestinalepithelialcellssynthesizeglucocorticoidsandregulatetcellactivation AT corazzanadia intestinalepithelialcellssynthesizeglucocorticoidsandregulatetcellactivation AT dickbernhard intestinalepithelialcellssynthesizeglucocorticoidsandregulatetcellactivation AT fuhrerandrea intestinalepithelialcellssynthesizeglucocorticoidsandregulatetcellactivation AT herrensimon intestinalepithelialcellssynthesizeglucocorticoidsandregulatetcellactivation AT jakobsabine intestinalepithelialcellssynthesizeglucocorticoidsandregulatetcellactivation AT ayunierick intestinalepithelialcellssynthesizeglucocorticoidsandregulatetcellactivation AT muellerchristoph intestinalepithelialcellssynthesizeglucocorticoidsandregulatetcellactivation AT brunnerthomas intestinalepithelialcellssynthesizeglucocorticoidsandregulatetcellactivation |