Inflammatory/Immune Modulations by Old and New Glucocorticoids: From Cell to Medical Application

Dear Colleagues,

Despite their venerable age, glucocorticoids still challenge and surprise us. Their widespread use in clinical practice and their surprisingly tissue-specific actions in maintaining body homeostasis demand further studies to fully decipher their mechanisms of action. If we only consider the genomic and non-genomic effects of glucocorticoids, the long- and short-term effects of synthetic glucocorticoids, the opposite effects exerted on multiple types of immune cells, and their crucial roles in differentiation, apoptosis, and proliferation, we realize important questions remain to be addressed. In particular, the cross-talk between activated glucocorticoid receptor (GR) and GR interactome with other receptors and signaling molecules appears a field of undisclosed potentials.

At the cellular levels, some evidence suggests that glucocorticoids modulate differentiation and survival of regulatory T cells (Tregs) and tolerogenic macrophages (e.g., M2), possibly by shaping the long-term maturation of the immune system. These effects may have a favorable impact on the development of inflammatory and autoimmune diseases but, at the same time, a deleterious effect on cancer immunosurveillance and progression. Hence, the interactions between synthetic glucocorticoids and immunosuppressive/immunomodulatory biologics that are currently in use or still under investigation (e.g., anti-CD3 and IL-2 antibodies), as well as synthetic glucocorticoids and epigenetic drugs (e.g., histone deacetylase inhibitors), deserve to be investigated.

The growing awareness concerning the effects of glucocorticoids on neuroendocrine system and behavior has created an urgent need to investigate the glucocorticoid-dependent neural network shaping. The concern about the sexually dimorphic actions of glucocorticoids on neuroendocrine system and other tissues has been catching on from a theoretic point of view and soon will have an impact on the clinics. The glucocorticoid-dependent damage to the skin and the direct protection of numerous non-immune cell types from the deleterious effect of inflammation are well known, but the underlined mechanisms deserve more studies. Topical glucocorticoids, including inhalation corticosteroids (ICSs), play a crucial role in the treatment of asthma, inflammatory bowel disease (IBD) and skin diseases, but their mechanism of action and adverse effects are still under investigation. Finally, new molecules modulating the activity of GR or mimicking the effect of GR activation are investigated with interesting results.

My hope and my ambition are that this Special Issue of IJMS may summarize these issues and shed new light on some of these, thanks to the contribution and the outstanding scientific research of the best scientists working in the glucocorticoid field.

Assoc. Prof. Dr. Giuseppe Nocentini
Guest Editor

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