Intestinal Epithelial Cells Synthesize Glucocorticoids and Regulate T Cell Activation

作者：Igor Cima, Nadia Corazza, Bernhard Dick, Andrea Corinne Fuhrer, Simon Herren, Sabine Jakob, Erick Ayuni, Christoph Mueller, Thomas B. Brunner · 发表于：The Journal of Experimental Medicine · 年份：2004 · DOI：10.1084/jem.20031958 · 被引用次数：204 · 研究领域：Adrenal Hormones and Disorders、Immune Cell Function and Interaction、Hormonal Regulation and Hypertension

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.