Immunomodulatory activities of glucocorticoids: insights from transgenesis and gene targeting

The glucocorticoid receptor (GR) is involved in the regulation of numerous physiological processes. In the immune system, it is thought to participate in lymphocyte apoptosis, T cell development and inflammatory responses. The extensive use of synthetic glucocorticoids as anti-inflammatory, immunosuppressive and anti-neoplastic drugs underscores the importance of the GR in immunomodulation. However, notwithstanding the long history of GR research and the clinical use of glucocorticoids, many questions regarding their mode of action remain. The following review summarizes the molecular genetic approaches that were taken during the last decade to answer some of these questions. The use of transgenic and knock-out mice has enabled gain-of-function and loss-of-function mutations in the GR to be generated even in restricted cell-types. Furthermore, these techniques possess the great advantage of allowing GR activities to be studied in the living animal. Many new and exciting findings have thereby been generated but despite the enormous efforts of several laboratories, a complete picture on the role of GR in the immune system is only just emerging.