Context-Dependent Effect of Glucocorticoids on the Proliferation, Differentiation, and Apoptosis of Regulatory T Cells: A Review of the Empirical Evidence and Clinical Applications

Abstract

Glucocorticoids (GCs) are widely used to treat several diseases because of their powerful anti-inflammatory and immunomodulatory effects on immune cells and non-lymphoid tissues. The effects of GCs on T cells are the most relevant in this regard. In this review, we analyze how GCs modulate the survival, maturation, and differentiation of regulatory T (Treg) cell subsets into both murine models and humans. In this way, GCs change the Treg cell number with an impact on the mid-term and long-term efficacy of GC treatment. In vitro studies suggest that the GC-dependent expansion of Treg cells is relevant when they are activated. In agreement with this observation, the GC treatment of patients with established autoimmune, allergic, or (auto)inflammatory diseases causes an expansion of Treg cells. An exception to this appears to be the local GC treatment of psoriatic lesions. Moreover, the effects on Treg number in patients with multiple sclerosis are uncertain. The effects of GCs on Treg cell number in healthy/diseased subjects treated with or exposed to allergens/antigens appear to be context-dependent. Considering the relevance of this effect in the maturation of the immune system (tolerogenic response to antigens), the success of vaccination (including desensitization), and the tolerance to xenografts, the findings must be considered when planning GC treatment.

Reformulating Small Molecules for Cardiovascular Disease Immune Intervention: Low-Dose Combined Vitamin D/Dexamethasone Promotes IL-10 Production and Atheroprotection in Dyslipidemic Mice

“…Current therapeutic use of VitD and Dexa in the clinical practice (high dose, oral/muscular delivery) implies systemic distribution with the expected consequences, beneficial and toxic, dictated by the pharmacological response of the ubiquitously expressed VDR and GR (35)(36)(37). Given the physical-chemical properties (very low water solubility) we reasoned that local (e.g., footpad, sc route) low-dose (10 µg) treatment using a repetitive but spaced scheme (rounds every other week) would provide biologically relevant concentrations of VitD/Dexa at local/regional level rather than systemically, restricting their effects to the site of injection and dLN.…”

Dexamethasone induces aberrant macrophage immune function and apoptosis

“…GCs have been used for the early treatment of rheumatoid arthritis, and have since become the most common therapy for inflammatory disorders (4). GCs remain very effective anti-inflammatory and immunosuppressive agents used in the treatment of numerous autoimmune diseases (1). However, recent research has suggested that chronic use of GCs is associated with tumorigenesis.…”

“…Glucocorticoids (GCs) are essential circadian steroid hormones that regulate perinatal development, memory, immune system function, and metabolism, as well as process emotional input (1) GCs are frequently used to treat rheumatoid arthritis due to their potent anti-inflammatory effect. The potent immunosuppressive effects of GCs are mediated by a series of transcriptional events, primarily by binding to the cytosolic glucocorticoid receptor (GR).…”

CD4+FOXP3+ T Cells in Rheumatoid Arthritis Bone Marrow Are Partially Impaired

“…In vitro studies indicate that glucocorticoids (GC) favor the expansion of activated Treg cells which are saved from apoptosis and stimulate differentiation of CD4 + cells into pTreg [52]. On the other side, GC determine the apoptosis of resting Tregs.…”