Glucocorticoid hormone treatment enhances the cytokine production of regulatory T cells by upregulation of Foxp3 expression

Ugor, Emese; Prenek, Lilla; Pap, Ramóna; Berta, Gergely; Ernszt, Dávid; Najbauer, Joseph; Németh, Pèter; Boldizsár, Ferenc; Berki, Tímea

doi:10.1016/j.imbio.2017.10.010

Cited by 42 publications

(33 citation statements)

References 64 publications

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“…The engagement of glucocorticoid receptor has been recently shown as crucial determinant conferring protection from autoimmunity during pregnancy in mice [36]. Regulatory T cells (Tregs) are particularly responsive to glucocorticoid signals [37] and impairment of Tregs has been described in a number of autoimmune diseases [38]. Interestingly, disrupted Tregs function has been reported in GSDIb patients [39].…”

Section: Discussionmentioning

confidence: 99%

Imbalanced cortisol concentrations in glycogen storage disease type I: evidence for a possible link between endocrine regulation and metabolic derangement

Rossi

Simeoli

Salerno

et al. 2020

Orphanet J Rare Dis

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Background: Glycogen storage disease type I (GSDI) is an inborn error of carbohydrate metabolism caused by mutations of either the G6PC gene (GSDIa) or the SLC37A4 gene (GSDIb). Glucose 6-phosphate (G6P) availability has been shown to modulate 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), an ER-bound enzyme catalyzing the local conversion of inactive cortisone into active cortisol. Adrenal cortex assessment has never been performed in GSDI. The aim of the current study was to evaluate the adrenal cortex hormones levels in GSDI patients. Methods: Seventeen GSDI (10 GSDIa and 7 GSDIb) patients and thirty-four age and sex-matched controls were enrolled. Baseline adrenal cortex hormones and biochemical markers of metabolic control serum levels were analyzed. Low dose ACTH stimulation test was also performed. Results: Baseline cortisol serum levels were higher in GSDIa patients (p = 0.042) and lower in GSDIb patients (p = 0.041) than controls. GSDIa patients also showed higher peak cortisol response (p = 0.000) and Cortisol AUC (p = 0.029). In GSDIa patients, serum cholesterol (p = 0.000), triglycerides (p = 0.000), lactate (p = 0.000) and uric acid (p = 0.008) levels were higher and bicarbonate (p = 0.000) levels were lower than controls. In GSDIb patients, serum cholesterol levels (p = 0.016) were lower and lactate (p = 0.000) and uric acid (p = 0.000) levels were higher than controls. Baseline cortisol serum levels directly correlated with cholesterol (ρ = 0.65, p = 0.005) and triglycerides (ρ = 0.60, p = 0.012) serum levels in GSDI patients. Conclusions: The present study showed impaired cortisol levels in GSDI patients, with opposite trend between GSDIa and GSDIb. The otherwise preserved adrenal cortex function suggests that this finding might be secondary to local deregulation rather than hypothalamo-pituitary-adrenal axis dysfunction in GSDI patients. We hypothesize that 11βHSD1 might represent the link between endocrine regulation and metabolic derangement in GSDI, constituting new potential therapeutic target in GSDI patients.

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Section: Discussionmentioning

confidence: 99%

Imbalanced cortisol concentrations in glycogen storage disease type I: evidence for a possible link between endocrine regulation and metabolic derangement

Rossi

Simeoli

Salerno

et al. 2020

Orphanet J Rare Dis

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“…There have been many reports involving GC and/or GR expression and immune suppression, mainly with T-cell differentiation and function (29,38). Meanwhile, the effects of B-cell differentiation and function are not as well investigated and are less controversial.…”

Section: Discussionmentioning

confidence: 99%

“…As GC signal is important for T-cell regulation (29,32), we hypothesized that IL-4 affected the decrease in GC signal. Therefore, we measured the concentration of GC and the expression of the GR in human lymphocytes, which affects GC signaling in T cells and B cells.…”

Section: Glucocorticoid Receptor Expression Negatively Correlates Witmentioning

confidence: 99%

“…The glucocorticoid receptor (GR), a steroid hormone receptor (24)(25)(26), is expressed in lymphocytes and is well known as a powerful immune regulator that can control GVHD symptoms (27)(28)(29). Therefore, glucocorticoid (GC) might play an important role in the suppression of GVHD symptoms in NOG and NOG-hIL-4-Tg mice transplanted with human PBMCs.…”

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confidence: 99%

“…This finding suggests that the highly expressed GC may inhibit specific IgG production in the NOG-based humanized mouse. Moreover, the effect of GC is still controversial on Treg-or Tfh-cell development (29,32).…”

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confidence: 99%

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Expression of glucocorticoid receptor shows negative correlation with human B-cell engraftment in PBMC-transplanted NOGhIL-4-Tg mice

Seki

Miyamoto

Ohshima

et al. 2018

BST

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The humanized mouse system is a promising tool for analyzing human immune responses in vivo. Recently, we developed a new humanized mouse system using the severely immunodeficient NOD/Shi-scid-IL2rγ (NOG)-hIL-4-Tg mouse, which enabled us to evaluate the human humoral immune response after peripheral blood mononuclear cell (PBMC) transplantation. However, the mechanism by which hIL-4 enhances antigen-specific IgG production in these mice is not clear. In this study, we analyzed the relationship between human lymphocyte subsets and the expression level of the glucocorticoid receptor (GR) to clarify the humoral immune condition in human PBMC-transplanted NOG-hIL-4 mice. The results showed that the human GR mRNA level was significantly lower in NOG-hIL-4-Tg splenocytes than in conventional NOG splenocytes after immunization. Whereas no obvious difference of the proportion of T helper-cell subsets was observed between the NOG and NOG-hIL-4-Tg mouse strains, the B-cell proportion and antigen-specific IgG concentration in plasma showed strong negative correlations with the GR mRNA level. These results suggest that the GR expression level was changed in PBMCs in the humanized NOG-hIL-4-Tg mice, which may support B-cell survival and function in the mouse system.

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The Pursuit of Regulatory T Cells in the Induction of Transplant Tolerance

Arnold

2021

Advances in Experimental Medicine and Biology

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Glucocorticoid hormone treatment enhances the cytokine production of regulatory T cells by upregulation of Foxp3 expression

Abstract: Our data show selective survival of tTregs and elevated production of immunosuppressive cytokines by Treg cells after GC treatment, which may contribute to the immunosuppressive effects of GCs.

Cited by 42 publications

References 64 publications

Imbalanced cortisol concentrations in glycogen storage disease type I: evidence for a possible link between endocrine regulation and metabolic derangement

Imbalanced cortisol concentrations in glycogen storage disease type I: evidence for a possible link between endocrine regulation and metabolic derangement

Expression of glucocorticoid receptor shows negative correlation with human B-cell engraftment in PBMC-transplanted NOGhIL-4-Tg mice

The Pursuit of Regulatory T Cells in the Induction of Transplant Tolerance

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