The Journal of Experimental Medicine
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Published online 13 December 2004 doi:10.1084/jem.20031958
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 12, 1635-1646
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Intestinal Epithelial Cells Synthesize Glucocorticoids and Regulate T Cell Activation

Igor Cima1, Nadia Corazza1, Bernhard Dick2, Andrea Fuhrer1, Simon Herren1, Sabine Jakob1, Erick Ayuni3, Christoph Mueller1, and Thomas Brunner1

1 Division of Immunopathology, Institute of Pathology, University of Bern, 3010 Bern, Switzerland
2 Division of Nephrology and Hypertension, Insel University Hospital and3 Division of Visceral and Transplant Surgery, Insel University Hospital, 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: tbrunner{at}pathology.unibe.ch

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-{gamma} 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.

Key Words: mucosal immunology • intraepithelial lymphocytes • costimulation • extraadrenal glucocorticoid synthesis • immune regulation

Abbreviations used in this paper: GC, glucocorticoid; GR, GC receptor; IEL, intraepithelial lymphocyte; LCMV, lymphocytic choriomeningitis virus; PPL, Peyer's patch lymphocyte; tg, transgenic.


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