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 (2004). Intestinal epithelial cells synthesize glucocorticoids and regulate T cell activation. Journal of experimental medicine, 200(12), pp. 1635-1646. Rockefeller University Press 10.1084/jem.20031958

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology

UniBE Contributor:

Cima, Igor; Corazza, Nadia; Dick, Bernhard; Fuhrer, Andrea; Müller, Christoph and Brunner, Thomas

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0022-1007

Publisher:

Rockefeller University Press

Language:

English

Submitter:

Christoph Müller

Date Deposited:

23 Sep 2022 11:07

Last Modified:

23 Sep 2022 11:17

Publisher DOI:

10.1084/jem.20031958

PubMed ID:

15596520

BORIS DOI:

10.48350/173179

URI:

https://boris.unibe.ch/id/eprint/173179

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