Glucocorticoids (GCs), which are produced by the cortex of the adrenal glands, are involved in the physiological regulation of a variety of processes including immune responses, metabolism, cell growth, and development. In line with this, GCs are part of the first-line medical treatment for numerous autoimmune and inflammatory diseases, such as asthma, rheumatoid arthritis, psoriasis and eczema. In the US, there are at least 80 million drug prescriptions annually that contain GCs as an active drug. Numerous synthetic versions of GCs have been developed, with their success being driven by their broad applicability, high efficacy and low cost. However, the complexity of their mechanism(s) of action and their various effects on different organs and cells, including the immune system, justify the wide interest of the scientific and medical community, who continue to discover new aspects of the effects, molecular mechanisms of action, and interactions of GCs.
For instance, the mechanisms by which GCs exert immune-suppressive and anti-inflammatory functions remains poorly understood. GCs induce their biological effects by binding to the glucocorticoid receptor (GR), which is responsible for regulating the transcription of genes containing Glucocorticoid Responsive Elements (GRE). In addition, the GR can also physically associate with other transcription factors to modulate a myriad of signaling pathways. With respect to the immune system, the GR may be involved (primarily as monomer) in protein-protein interactions with transcription factors, such as NF-kB, AP1, STATs, IRFs, etc., leading to the inhibition of proinflammatory cytokine expression and modulation of related immune-signalling pathways. Another mechanism by which GCs exert anti-inflammatory effects involves transcriptional activation of molecules such as Glucocorticoid-Induced-Leucine-Zipper (GILZ), dual-specificity protein phosphatase 1 (DUSP1) or annexin-1 (Anx1), which can mediate immunosuppressive and anti-inflammatory effects by interfering with inflammation-activated pathways, such as NF-kB, DUSP1 or the eicosanoid cascade as well as by influencing the maturation and/or proliferation of specific T-cell populations, e.g. regulatory T cells in the case of GILZ.
Based on these considerations, this Research Topic aims to cover the current understanding of and recent advances in research on GCs in regulating inflammation and related immune responses. We welcome the submission of Original Research articles and Reviews with a core immunological focus that cover, but are not limited to, the following topics:
(1) Molecular mechanisms of how GCs and GR modulate the immune system
(2) Application of GCs for the treatment of autoimmune and inflammatory diseases, such as psoriasis, asthma, COPD and rheumatoid arthritis
(3) Studies of the effects and mechanisms of action of GCs in the treatment of diseases and disease models of immune dysfunction
(4) Novel treatment strategies for immune diseases targeting GCs and GR
(5) Immunological mechanisms underlying GC side effects after chronic GC therapy
(6) Resistance to GC treatment in immune diseases developed in cells of the innate and adaptive immune system
Glucocorticoids (GCs), which are produced by the cortex of the adrenal glands, are involved in the physiological regulation of a variety of processes including immune responses, metabolism, cell growth, and development. In line with this, GCs are part of the first-line medical treatment for numerous autoimmune and inflammatory diseases, such as asthma, rheumatoid arthritis, psoriasis and eczema. In the US, there are at least 80 million drug prescriptions annually that contain GCs as an active drug. Numerous synthetic versions of GCs have been developed, with their success being driven by their broad applicability, high efficacy and low cost. However, the complexity of their mechanism(s) of action and their various effects on different organs and cells, including the immune system, justify the wide interest of the scientific and medical community, who continue to discover new aspects of the effects, molecular mechanisms of action, and interactions of GCs.
For instance, the mechanisms by which GCs exert immune-suppressive and anti-inflammatory functions remains poorly understood. GCs induce their biological effects by binding to the glucocorticoid receptor (GR), which is responsible for regulating the transcription of genes containing Glucocorticoid Responsive Elements (GRE). In addition, the GR can also physically associate with other transcription factors to modulate a myriad of signaling pathways. With respect to the immune system, the GR may be involved (primarily as monomer) in protein-protein interactions with transcription factors, such as NF-kB, AP1, STATs, IRFs, etc., leading to the inhibition of proinflammatory cytokine expression and modulation of related immune-signalling pathways. Another mechanism by which GCs exert anti-inflammatory effects involves transcriptional activation of molecules such as Glucocorticoid-Induced-Leucine-Zipper (GILZ), dual-specificity protein phosphatase 1 (DUSP1) or annexin-1 (Anx1), which can mediate immunosuppressive and anti-inflammatory effects by interfering with inflammation-activated pathways, such as NF-kB, DUSP1 or the eicosanoid cascade as well as by influencing the maturation and/or proliferation of specific T-cell populations, e.g. regulatory T cells in the case of GILZ.
Based on these considerations, this Research Topic aims to cover the current understanding of and recent advances in research on GCs in regulating inflammation and related immune responses. We welcome the submission of Original Research articles and Reviews with a core immunological focus that cover, but are not limited to, the following topics:
(1) Molecular mechanisms of how GCs and GR modulate the immune system
(2) Application of GCs for the treatment of autoimmune and inflammatory diseases, such as psoriasis, asthma, COPD and rheumatoid arthritis
(3) Studies of the effects and mechanisms of action of GCs in the treatment of diseases and disease models of immune dysfunction
(4) Novel treatment strategies for immune diseases targeting GCs and GR
(5) Immunological mechanisms underlying GC side effects after chronic GC therapy
(6) Resistance to GC treatment in immune diseases developed in cells of the innate and adaptive immune system
