Glucocorticoid receptor mediated suppression of natural killer cell activity: Identification of associated deacetylase and corepressor molecules

Bush, Kristin A.; Krukowski, Karen; Eddy, Justin L.; Janusek, Linda Witek; Mathews, Herbert L.

doi:10.1016/j.cellimm.2012.02.014

Cited by 42 publications

(37 citation statements)

References 47 publications

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“…The mechanism by which mental dysfunction acts on NK cells is still debated. Many hypotheses are proposed, including the deregulation of the hypothalamic/pituitary/adrenal axis leading to elevated levels of blood glucocorticoids, which further inhibit NKCA through epigenetic processes (75). Several other mental disorders are correlated with a diminution of NK cell functions, such as obsessive-compulsive disorder (76) and autism (77).…”

Section: Nk Cell Modifications Associated With Cns Disordersmentioning

confidence: 99%

NK Cells in Central Nervous System Disorders

Poli

Kmiecik

Domingues

et al. 2013

The Journal of Immunology

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NK cells are important players in immunity against pathogens and neoplasms. As a component of the innate immune system, they are one of the first effectors on sites of inflammation. Through their cytokine production capacities, NK cells participate in the development of a potent adaptive immune response. Furthermore, NK cells were found to have regulatory functions to limit and prevent autoimmunity via killing of autologous immune cells. These paradoxical functions of NK cells are reflected in CNS disorders. In this review, we discuss the phenotypes and functional features of peripheral and brain NK cells in brain tumors and infections, neurodegenerative diseases, acute vascular and traumatic damage, as well as mental disorders. We also discuss the implication of NK cells in neurotoxicity and neuroprotection following CNS pathology, as well as the crosstalk between NK cells and brain-resident immune cells.

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Section: Nk Cell Modifications Associated With Cns Disordersmentioning

confidence: 99%

NK Cells in Central Nervous System Disorders

Poli

Kmiecik

Domingues

et al. 2013

The Journal of Immunology

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“…48 The basic immune model of Folcik et al 38 was also extended to include the hormonal actions of CORT and TEST. CORT is a potent modulator of immune function suppressing NK cell activity, 49 Th1 activity, 50 and inflammatory DC activity. 51 Additionally, CORT acts on naïve T-cells to repress both the Th1 promoting transcription factor, T-bet, and the Th2 promoting transcription factor, GATA-3.…”

Section: Literature-based Immune Signaling Networkmentioning

confidence: 99%

Succumbing to the laws of attraction

Fritsch

Craddock

Rosario

et al. 2013

Systems Biomedicine

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systems Biomedicine Volume 1 Issue 3 PF, TJAC, RMdR, and MAR performed computational simulations and analysis of computational results. PF, TJAC, ALS, VAF, and GB, compiled physiological data and developed the immune-endocrine connectivity network. PF, TJAC, and GB performed comparisons between experimental and computational data and interpreted the results. MAF and NGK collected and analyzed the experimental data. TJAC, RMdR, MAR, GdV, and GB conceived of the discrete logical analysis algorithm. All authors contributed to the drafting of this article, and approve of its contents.

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“…Human NK cells have also been shown to proliferate in response to a [17]. In contrast, a recent study demonstrated GR-mediated inhibition of NK cell activity [18]. Moreover, it has been shown that GCs disregulate NK cell functions through epigenetic modification [19].…”

Section: Introductionmentioning

confidence: 99%

The selective impact of transgenically expressed glucocorticoid receptor on T cells

et al. 2014

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Glucocorticoids (GCs) strongly impact on different T cell subsets inducing generally immunosuppressive effects, whereas much less is known about the effect of GC on natural killer (NK) cells. The aims of this study were to investigate the effects of GC on T cell functions, including T cell-mediated anti-tumor immune response, and on NK cells. We have used lck-GR mice, which overexpress a transgenic rat GR in both T and NK cells. These mice were found to have decreased both CD4(+) and CD8(+) T cell populations in the periphery. In contrast, both NK and NKT cells were found in normal numbers in lck-GR mice. To identify genes and pathways affected by GR overexpression in our system in T cells, we have compared gene expression profiles in wild-type and lck-GR T cells. Among the genes upregulated in T cells from lck-GR mice, the microarray analysis has identified genes regulating expansion of regulatory T cells. The analysis of genes downregulated in lck-GR mice has identified genes and gene associated with the regulation of immune response. With regard to the effects on T cell functions in lck-GR mice, transgenic expression of GR had a suppressive effect on killer cell activity in vitro. In addition, lck-GR mice showed an increased tumor growth in murine tumor model in vivo, which may be a possible consequence of reduced T cell numbers and activity. We conclude that an increased expression of the GR strongly affects numbers and possibly functions of T cell subsets, but has little effect on NK cells.

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Glucocorticoid receptor mediated suppression of natural killer cell activity: Identification of associated deacetylase and corepressor molecules

Cited by 42 publications

References 47 publications

NK Cells in Central Nervous System Disorders

NK Cells in Central Nervous System Disorders

Succumbing to the laws of attraction

The selective impact of transgenically expressed glucocorticoid receptor on T cells

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