LXR Nuclear receptors are transcriptional regulators of dendritic cell chemotaxis

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 respons...

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Detalles Bibliográficos
Autores: Beceiro, Susana, Pap, Attila, Czimmerer, Zsolt, Sallam, Tamer, Guillén, Jose A., Gallardo, Germán, Hong, Cynthia, A-Gonzalez, Noelia, Tabraue, Carlos, Diaz, Mercedes, Lopez, Felix, Matalonga, Jonathan, Valledor Fernández, Annabel, Dominguez, Pilar, Ardavin, Carlos, Delgado-Martin, Cristina, Partida-Sanchez, Santiago, Rodriguez-Fernandez, Jose Luis, Nagy, Laszlo, Tontonoz, Peter, Castrillo, Antonio
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2018
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/189791
Acceso en línea:https://hdl.handle.net/2445/189791
Access Level:acceso abierto
Palabra clave:Quimiotaxi
Cèl·lules dendrítiques
Inflamació
Macròfags
Receptors nuclears (Bioquímica)
Transducció de senyal cel·lular
Chemotaxis
Dendritic cells
Inflammation
Macrophages
Nuclear receptors (Biochemistry)
Cellular signal transduction
Descripción
Sumario: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.

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