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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20 December 2004
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December 13 2004
Intestinal Epithelial Cells Synthesize Glucocorticoids and Regulate T Cell Activation
Igor Cima,
Igor Cima
1Division of Immunopathology, Institute of Pathology, University of Bern, 3010 Bern, Switzerland
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Nadia Corazza,
Nadia Corazza
1Division of Immunopathology, Institute of Pathology, University of Bern, 3010 Bern, Switzerland
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Bernhard Dick,
Bernhard Dick
2Division of Nephrology and Hypertension, Insel University Hospital
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Andrea Fuhrer,
Andrea Fuhrer
1Division of Immunopathology, Institute of Pathology, University of Bern, 3010 Bern, Switzerland
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Simon Herren,
Simon Herren
1Division of Immunopathology, Institute of Pathology, University of Bern, 3010 Bern, Switzerland
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Sabine Jakob,
Sabine Jakob
1Division of Immunopathology, Institute of Pathology, University of Bern, 3010 Bern, Switzerland
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Erick Ayuni,
Erick Ayuni
3Division of Visceral and Transplant Surgery, Insel University Hospital, 3010 Bern, Switzerl
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Christoph Mueller,
Christoph Mueller
1Division of Immunopathology, Institute of Pathology, University of Bern, 3010 Bern, Switzerland
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Thomas Brunner
Thomas Brunner
1Division of Immunopathology, Institute of Pathology, University of Bern, 3010 Bern, Switzerland
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Igor Cima
1Division of Immunopathology, Institute of Pathology, University of Bern, 3010 Bern, Switzerland
Nadia Corazza
1Division of Immunopathology, Institute of Pathology, University of Bern, 3010 Bern, Switzerland
Bernhard Dick
2Division of Nephrology and Hypertension, Insel University Hospital
Andrea Fuhrer
1Division of Immunopathology, Institute of Pathology, University of Bern, 3010 Bern, Switzerland
Simon Herren
1Division of Immunopathology, Institute of Pathology, University of Bern, 3010 Bern, Switzerland
Sabine Jakob
1Division of Immunopathology, Institute of Pathology, University of Bern, 3010 Bern, Switzerland
Erick Ayuni
3Division of Visceral and Transplant Surgery, Insel University Hospital, 3010 Bern, Switzerl
Christoph Mueller
1Division of Immunopathology, Institute of Pathology, University of Bern, 3010 Bern, Switzerland
Thomas Brunner
1Division of Immunopathology, Institute of Pathology, University of Bern, 3010 Bern, Switzerland
Address correspondence to Thomas Brunner, Div. of Immunopathology, Institute of Pathology, PO Box 62, Murtenstrasse 31, 3010 Bern, Switzerland. Phone: 41-31-632-49-71; Fax: 41-31-381-87-64; email: [email protected]
Abbreviations used in this paper: GC, glucocorticoid; GR, GC receptor; IEL, intraepithelial lymphocyte; LCMV, lymphocytic choriomeningitis virus; PPL, Peyer's patch lymphocyte; tg, transgenic.
Received:
November 13 2003
Accepted:
October 13 2004
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2004
J Exp Med (2004) 200 (12): 1635–1646.
Article history
Received:
November 13 2003
Accepted:
October 13 2004
Citation
Igor Cima, Nadia Corazza, Bernhard Dick, Andrea Fuhrer, Simon Herren, Sabine Jakob, Erick Ayuni, Christoph Mueller, Thomas Brunner; Intestinal Epithelial Cells Synthesize Glucocorticoids and Regulate T Cell Activation . J Exp Med 20 December 2004; 200 (12): 1635–1646. doi: https://doi.org/10.1084/jem.20031958
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