Glucocorticoids in T cell development, differentiation and function

Glucocorticoid treatment is used to suppress the immune system in various disease settings. However, endogenous glucocorticoids are able to promote as well as inhibit different aspects of T cell immunity. Here, the authors discuss the many ways in which T cell responses are shaped by glucocorticoids. Glucocorticoids (GCs) are small lipid hormones produced by the adrenals that maintain organismal homeostasis. Circadian and stress-induced changes in systemic GC levels regulate metabolism, cardiovascular and neural function, reproduction and immune activity. Our understanding of GC effects on immunity comes largely from administration of exogenous GCs to treat immune or inflammatory disorders. However, it is increasingly clear that endogenous GCs both promote and suppress T cell immunity. Examples include selecting an appropriate repertoire of T cell receptor (TCR) self-affinities in the thymus, regulating T cell trafficking between anatomical compartments, suppressing type 1 T helper (T(H)1) cell responses while permitting T(H)2 cell and, especially, IL-17-producing T helper cell responses, and promoting memory T cell differentiation and maintenance. Furthermore, in addition to functioning at a distance, extra-adrenal (local) production allows GCs to act as paracrine signals, specifically targeting activated T cells in various contexts in the thymus, mucosa and tumours. These pleiotropic effects on different T cell populations during development and immune responses provide a nuanced understanding of how GCs shape immunity.

Automated summary

Glucocorticoids have dual effects on the immune system, promoting and suppressing T cell immunity. They shape T cell responses in various ways, such as selecting appropriate T cell receptor self-affinities and regulating T cell trafficking between anatomical compartments.