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 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.
Cima
Igor
I
Div. of Immunopathology, Institute of Pathology, PO Box 62, Murtenstrasse 31, 3010 Bern, Switzerland.
Corazza
Nadia
N
Dick
Bernhard
B
Fuhrer
Andrea
A
Herren
Simon
S
Jakob
Sabine
S
Ayuni
Erick
E
Mueller
Christoph
C
Brunner
Thomas
T
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D001117:Arenaviridae Infections / Q000276:immunology / Q000473:pathology; D017252:CD3 Complex / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D005938:Glucocorticoids / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000378:metabolism*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*; D000099192:CD69 Antigens
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D005938:Glucocorticoids; D007371:Interferon-gamma; D037181:Lectins, C-Type; D000099192:CD69 Antigens