Liver X Receptors Control IgE Expression in B Cells

Heine, Guido; Dahten, Anja; Hilt, Kerstin; Ernst, Dennis; Milovanović, M; Hartmann, Björn; Worm, Margitta

doi:10.4049/jimmunol.0801804

Cited by 53 publications

(45 citation statements)

References 38 publications

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“…As an example, activation of LXRs by TO901317 reduced secreted IgE in activated B lymphocytes, without affecting IgE class switch recombination or its transcription. LXR activation resulted in reduced phosphorylation of c-Jun N-terminal kinase 2 and increased membrane expression of CD23, the low-affinity receptor for IgE, which helps reduce IgE secretion as a negative feedback loop (Heine et al 2009). …”

Section: Lxrs As Negative Regulators Of Inflammationmentioning

confidence: 99%

Biological Roles of Liver X Receptors in Immune Cells

Pascual-García

Valledor

2012

Arch. Immunol. Ther. Exp.

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Liver X receptors (LXRs) are members of the nuclear receptor superfamily that are activated by specific oxysterols. LXRs heterodimerize with retinoid X receptors to regulate positively the expression of a variety of target genes, many of which are involved in lipid and glucose metabolism. In the last few years, new targets of LXR activation have been identified with roles in the modulation of immune responses. Moreover, LXRs mediate repression of inflammatory pathways through mechanisms collectively known as transrepression. Here, we revise recent findings on the impact of LXR activation on immune responses, with an emphasis on advances in the understanding of the molecular mechanisms that mediate these effects.

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Section: Lxrs As Negative Regulators Of Inflammationmentioning

confidence: 99%

Biological Roles of Liver X Receptors in Immune Cells

Pascual-García

Valledor

2012

Arch. Immunol. Ther. Exp.

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“…Additionally, LXRs have a role in the differentiation of different CD4 T cells subsets; LXR agonists inhibit the Th17 differentiation through a mechanism that involves Srebp1c/Aryl hydrocarbon receptor-mediated inhibition IL17 expression [135,145]. LXR agonists have also been described to inhibit IgE production in human and murine B cells [146]. Oxysterols are also agonists for RORγt, which is required for Th17 T cell differentiation.…”

Section: Oxysterols As Ligands For Nuclear Receptorsmentioning

confidence: 99%

Nutrient sensing, signal transduction and immune responses

Walls

Sinclair

Finlay

2016

Seminars in Immunology

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Most cells in the body have a constant supply of nutrients, which are required to sustain cellular metabolism and functions. In contrast, cells of the immune system can encounter conditions with a limited nutrient supply during the course of an immune response. Cells of the immune system frequently operate in complex nutrient restricted microenvironments such as tumour or inflammatory sites. The concentrations of key nutrients such as glucose and certain amino acids, can be low at these sites, and this can have an impact upon immune cell function. Nutrient sufficiency is important to supply the metabolic and biosynthetic pathways of immune cells. In addition nutrients can also act as important cues that influence immunological signalling pathways to affect the function of immune cells. This review will describe the various nutrient sensing signalling pathways and discuss the evidence that nutrients are critical signals that shape immune responses.

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“…LXR activation promotes potent antiinflammatory effects in B cells, T cells, neutrophils, macrophages and DC. [4][5][6][7][8] Furthermore, LXR expression has been linked to inflammatory bowel disease (IBD) where polymorphisms in the LXR gene have been strongly associated with an individual's susceptibility to ulcerative colitis. 9 Previous studies have also highlighted a reciprocal relationship between the nuclear receptor pathway and the TLR pathway, where activation of one leads to the inhibition of the other.…”

Section: Introductionmentioning

confidence: 99%

Activation of liver X receptor suppresses the production of the IL-12 family of cytokines by blocking nuclear translocation of NF-κBp50

et al. 2013

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There is now convincing evidence that liver X receptor (LXR) is an important modulator of the inflammatory response; however, its mechanism of action remains unclear. This study aimed to examine the effect of LXR on the IL-12 family of cytokines and examined the mechanism by which LXR exerted this effect. We first demonstrated that activation of murine-derived dendritic cells (DC) with a specific agonist to LXR enhanced expression of LXR following activation with LPS, suggesting a role in inflammation. Furthermore, we showed LXR expression to be increased in vivo in dextrane sulphate sodium-induced colitis. LXR activation also suppressed production of IL-12p40, IL-12p70, IL-27 and IL-23 in murine-derived DC following stimulation with LPS, and specifically targeted the p35, p40 and EBI3 subunits of the IL-12 cytokine family, which are under the control of the NF-kB subunit p50 (NF-kBp50). Finally, we demonstrated that LXR can associate with NF-kBp50 in DC and that LXR activation prevents translocation of the p50 subunit into the nucleus. In summary, our study indicates that LXR can specifically suppress the IL-12 family of cytokines though its association with NF-kBp50 and highlights its potential as a therapeutic target for chronic inflammatory diseases.

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Liver X Receptors Control IgE Expression in B Cells

Cited by 53 publications

References 38 publications

Biological Roles of Liver X Receptors in Immune Cells

Biological Roles of Liver X Receptors in Immune Cells

Nutrient sensing, signal transduction and immune responses

Activation of liver X receptor suppresses the production of the IL-12 family of cytokines by blocking nuclear translocation of NF-κBp50

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