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Intestinal epithelial cells synthesize glucocorticoids and regulate T cell activation
Igor Cima1, Nadia Corazza, Bernhard Dick
1Div. of Immunopathology, Institute of Pathology, PO Box 62, Murtenstrasse 31, 3010 Bern, Switzerland.
The Journal of Experimental Medicine
|December 15, 2004
Summary
The gut lining can produce glucocorticoids (GCs), important immune-regulating hormones. Intestinal GCs play a dual role in T cell activation, influencing immune responses to different stimuli.
Area of Science:
- Endocrinology
- Immunology
- Gastroenterology
Background:
- Glucocorticoids (GCs) are crucial steroid hormones regulating metabolism, development, and immunity.
- Adrenal glands are the primary source of GCs, released during stress.
- Emerging evidence suggests nonadrenal tissue synthesis of GCs.
Purpose of the Study:
- To investigate if the intestinal mucosa synthesizes glucocorticoids.
- To determine the role of locally produced GCs in intestinal T cell activation.
Main Methods:
- In situ hybridization to localize steroidogenic enzymes in the intestinal mucosa.
- Analysis of T cell activation markers (CD69, interferon-gamma) in the presence and absence of intestinal GCs.
- In vivo studies using anti-CD3 injection and viral infection models.
Main Results:
- The intestinal mucosa expresses key steroidogenic enzymes, particularly in the crypt region.
- T cell activation upregulates the expression of these enzymes.
- Intestinal GCs exhibit context-dependent roles: inhibitory for anti-CD3 activation, costimulatory for viral infection-induced activation.
- Absence of intestinal GCs altered T cell responses to stimuli.
Conclusions:
- The intestinal mucosa is a significant source of immunoregulatory glucocorticoids.
- Locally produced GCs modulate intestinal T cell responses in a stimulus-specific manner.