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Title: Liver X receptor nuclear receptors are transcriptional regulators of dendritic cell chemotaxis
Authors: Beceiro, Susana 
Pap, Attila
Czimmerer, Zsolt
Sallam, Tamer
Guillén Salgado, José Ángel 
Gallardo, Germán 
Hong, Cynthia
A-Gonzalez, Noelia
Tabraue, Carlos 
Díaz Sarmiento, María Mercedes 
López Blanco, Félix 
Matalong, Jonathan
Valledor, Annabel F.
Dominguez, Pilar
Ardavin, Carlos
Delgado-Martin, Cristina
Partida-Sanchez, Santiago
Rodriguez-Fernandez, Jose Luis
Nagy, Laszlo
Tontono, Peter
Castrillo, Antonio 
UNESCO Clasification: 32 Ciencias médicas
Keywords: CD38
Dendritic cells
Liver X receptor, et al
Issue Date: 2018
Journal: Molecular and Cellular Biology 
Abstract: The liver X receptors (LXRs) are ligand-activated nuclear receptors with established roles in the maintenance of lipid homeostasis in multiple tissues. LXRs exert additional biological functions as negative regulators of inflammation, particularly in macrophages. However, the transcriptional responses controlled by LXRs in other myeloid cells, such as dendritic cells (DCs), are still poorly understood. Here we used gain- and loss-of-function models to characterize the impact of LXR deficiency on DC activation programs. Our results identified an LXR-dependent pathway that is important for DC chemotaxis. LXR-deficient mature DCs are defective in stimulus-induced migration in vitro and in vivo. Mechanistically, we show that LXRs facilitate DC chemotactic signaling by regulating the expression of CD38, an ectoenzyme important for leukocyte trafficking. Pharmacological or genetic inactivation of CD38 activity abolished the LXR-dependent induction of DC chemotaxis. Using the low-density lipoprotein receptor-deficient (LDLR-/-) LDLR-/-mouse model of atherosclerosis, we also demonstrated that hematopoietic CD38 expression is important for the accumulation of lipid-laden myeloid cells in lesions, suggesting that CD38 is a key factor in leukocyte migration during atherogenesis. Collectively, our results demonstrate that LXRs are required for the efficient emigration of DCs in response to chemotactic signals during inflammation.
ISSN: 0270-7306
DOI: 10.1128/MCB.00534-17
Source: Molecular And Cellular Biology[ISSN 0270-7306],v. 38 (10)
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