Liver X Receptors Regulate Dendritic Cell Phenotype and Function Through Blocked Induction of the Actin-bundling Protein Fascin.
From: Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Austria.
Blood
- Publish Date: May 2007
- ISSN: 0006-4971
- Volume: 109
- Issue: 10
- Pages: 4288-95
- Medium: Print
- Language: English
- Citation (JAMA): Geyeregger René, Zeyda Maximilian, Bauer Wolfgang, et al. Liver X Receptors Regulate Dendritic Cell Phenotype and Function Through Blocked Induction of the Actin-bundling Protein Fascin.. Blood May 2007;109:4288-95
Abstract
Liver X receptors (LXRs) are nuclear receptors regulating lipid and cholesterol metabolism. Recent data revealed a cross talk between LXR and Toll-like receptor signaling in macrophages, indicating a role in immunity. Here, we show that LXRalpha is expressed in human myeloid dendritic cells (DCs) and induced during differentiation of monocyte-derived DCs, whereas LXRbeta is expressed constitutively at a very low level. LXR activation by 2 different LXR agonists strongly interfered with lipopolysaccharide (LPS)-induced but not with CD40L-induced DC maturation by altering DC morphology and suppressing interleukin-12-but enhancing interleukin-10-secretion. LXR activation in DCs largely blocked their T-cell stimulatory ability despite essentially unaltered expression of various antigen-presenting and costimulatory molecules. Immunologic synapse formation was significantly inhibited by LXR activation along with a complete block in LPS- but not CD40L-induced expression of the actin-bundling protein fascin. Notably, overexpression of fascin in LXR agonist-treated DCs restored immunologic synapse formation and restored their ability to activate T cells. In conclusion, our data reveal LXR as a potent modulator of DC maturation and function mediated in part by blocking the expression of fascin. Due to the central position of DCs in immunity, LXRalpha could be a potential novel target for immunomodulation.
Mesh Headings (Keywords): Carrier Proteins, Cells, Cultured, DNA-Binding Proteins, Dendritic Cells, Female, Gene Expression Regulation, Humans, Male, Microfilament Proteins, Phenotype, Receptors, Cytoplasmic and Nuclear, Sulfonamides, Transfection
Check for Full Text / PubMed Unique Identifier (PMID): 17255360
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