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http://hdl.handle.net/2445/189791
Title: | LXR Nuclear receptors are transcriptional regulators of dendritic cell chemotaxis |
Author: | 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 |
Keywords: | 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 |
Issue Date: | 5-Mar-2018 |
Publisher: | American Society for Microbiology |
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. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1128/MCB.00534-17 |
It is part of: | Molecular and Cellular Biology, 2018, vol. 38, num. 10, p. e00534-17 |
URI: | http://hdl.handle.net/2445/189791 |
Related resource: | https://doi.org/10.1128/MCB.00534-17 |
ISSN: | 0270-7306 |
Appears in Collections: | Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia) |
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