Clinically, glucocorticoids represent suppressive molecules of inflammatory immune response. During COVID-19 outbreak, the potent synthetic glucocorticoid Dexamethasone has become an important therapeutic tool in patients in later and severe stages of the disease, reassuring the usefulness of this class of anti-inflammatory drugs in the treatment of such devastating infectious disease. Steroidal regulation of both infectious and non-infectious inflammatory conditions is complex, including mechanisms involving classical DNA binding of engaged nuclear receptors in regulatory sequences of target genes, transrepression/activation, chromatin states, phase separation, epigenetics and receptor-independent pathways. A similar level of complexity might apply to other steroidal hormones, such as those involved in sexually dimorphic immune responses. In addition to well-known steroid hormones, i.e. glucocorticoids, aldosterone and vitamin D, aspects of non-canonical signaling of oxysteroids and cardiotonic steroids are important topics to be uncovered during control and treatment of an infectious and non-infectious inflammatory condition. Single-cell data and innovative approaches targeted to further dissect steroidal transcriptional regulation in a given tissue on these events are also of particular interest. Detailed aspects of general and tissue-specific effects of these different steroids in health and disease are of significant importance to address this research topic from a translational perspective.
Clinically, glucocorticoids represent suppressive molecules of inflammatory immune response. During COVID-19 outbreak, the potent synthetic glucocorticoid Dexamethasone has become an important therapeutic tool in patients in later and severe stages of the disease, reassuring the usefulness of this class of anti-inflammatory drugs in the treatment of such devastating infectious disease. Steroidal regulation of both infectious and non-infectious inflammatory conditions is complex, including mechanisms involving classical DNA binding of engaged nuclear receptors in regulatory sequences of target genes, transrepression/activation, chromatin states, phase separation, epigenetics and receptor-independent pathways. A similar level of complexity might apply to other steroidal hormones, such as those involved in sexually dimorphic immune responses. In addition to well-known steroid hormones, i.e. glucocorticoids, aldosterone and vitamin D, aspects of non-canonical signaling of oxysteroids and cardiotonic steroids are important topics to be uncovered during control and treatment of an infectious and non-infectious inflammatory condition. Single-cell data and innovative approaches targeted to further dissect steroidal transcriptional regulation in a given tissue on these events are also of particular interest. Detailed aspects of general and tissue-specific effects of these different steroids in health and disease are of significant importance to address this research topic from a translational perspective.
