Abstract
Glucocorticoids (GCs) are steroid hormones predominantly produced in the adrenal glands in response to physiological cues and stress. Adrenal GCs mediate potent anti-inflammatory and immunosuppressive functions. Accumulating evidence in the past two decades has demonstrated other extra-adrenal organs and tissues capable of synthesizing GCs. This review discusses the role and regulation of GC synthesis in the intestinal epithelium in the regulation of normal immune homeostasis, inflammatory diseases of the intestinal mucosa, and the development of intestinal tumors.
Highlights
The synthesis of adrenal GCs is regulated by the hypothalamic-pituitary-adrenal (HPA) axis (Figure 1), and controlled by the main circadian oscillator located in the suprachiasmatic nucleus (SCN) of the hypothalamus [1]
They showed that bioactive GCs are de novo synthesized by thymic epithelial cells (TECs), and that they play an important role in antigen-specific thymocyte development by opposing cell death induction from too strong T cell receptor (TCR) signaling during negative selection, thereby allowing positively selected T cells to survive
Increasing lines of evidence have shown that the synthesis of GCs by intestinal epithelial cell (IEC) plays an important role in the regulation of intestinal immune homeostasis under pathophysiological conditions [21, 77, 129, 130]
Summary
Glucocorticoids (GCs) are immunoregulatory hormones synthesized in the adrenal cortex and secreted into the blood in a circadian mode under physiological and stress conditions [1]. In the 1940s GCs were discovered as extracts of the adrenal cortex. This was followed by the isolation of adrenocorticotropic hormone (ACTH) from pituitary gland extracts. Since the 1950s, and owing to their strong anti-inflammatory and immunosuppressive activities, GCs have been widely used for the treatment of inflammatory disorders and autoimmune diseases, such as asthma, rheumatoid arthritis, dermatitis, inflammatory bowel disease (IBD), sepsis, lupus erythematosus, and multiple sclerosis [7,8,9,10,11]. Immunological, environmental, and emotional stress induces the release of GCs to mediate immunoregulatory activities, mostly immunosuppressive, on distant tissues and cells, in particular in immune cells [4]. GCs have an immunosuppressive activity on T cell-mediated immune responses [13] and this is why they are frequently used for the treatments of T cell-mediated immunopathologies
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