Miniatura

Fitxers

679478.pdf (3.42 MB)

Tipus de document

Article

Versió

Versió acceptada

Data de publicació

2018-03-05

Tots els drets reservats

Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/189791

LXR Nuclear receptors are transcriptional regulators of dendritic cell chemotaxis

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1128/MCB.00534-17

Resum

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.

Matèries

Quimiotaxi, Cèl·lules dendrítiques, Inflamació, Macròfags, Receptors nuclears (Bioquímica), Transducció de senyal cel·lular

Matèries (anglès)

Chemotaxis, Dendritic cells, Inflammation, Macrophages, Nuclear receptors (Biochemistry), Cellular signal transduction

Citació

Col·leccions

Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

Citació

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. LXR Nuclear receptors are transcriptional regulators of dendritic cell chemotaxis. _Molecular and Cellular Biology_. 2018. Vol. 38, núm. 10, pàgs. e00534-17. [consulta: 9 de gener de 2026]. ISSN: 0270-7306. [Disponible a: https://hdl.handle.net/2445/189791]

Exportar metadades

JSON - METS

Compartir registre