LXR Nuclear receptors are transcriptional regulators of dendritic cell chemotaxis

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

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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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

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network_acronym_str	ES
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spelling	LXR Nuclear receptors are transcriptional regulators of dendritic cell chemotaxisBeceiro, SusanaPap, AttilaCzimmerer, ZsoltSallam, TamerGuillén, Jose A.Gallardo, GermánHong, CynthiaA-Gonzalez, NoeliaTabraue, CarlosDiaz, MercedesLopez, FelixMatalonga, JonathanValledor Fernández, AnnabelDominguez, PilarArdavin, CarlosDelgado-Martin, CristinaPartida-Sanchez, SantiagoRodriguez-Fernandez, Jose LuisNagy, LaszloTontonoz, PeterCastrillo, AntonioQuimiotaxiCèl·lules dendrítiquesInflamacióMacròfagsReceptors nuclears (Bioquímica)Transducció de senyal cel·lularChemotaxisDendritic cellsInflammationMacrophagesNuclear receptors (Biochemistry)Cellular signal transductionThe 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.American Society for Microbiology2022202220182022info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion18 p.application/pdfhttps://hdl.handle.net/2445/189791Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1128/MCB.00534-17Molecular and Cellular Biology, 2018, vol. 38, num. 10, p. e00534-17https://doi.org/10.1128/MCB.00534-17(c) American Society for Microbiology, 2018info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1897912026-05-29T05:05:01Z
dc.title.none.fl_str_mv	LXR Nuclear receptors are transcriptional regulators of dendritic cell chemotaxis
title	LXR Nuclear receptors are transcriptional regulators of dendritic cell chemotaxis
spellingShingle	LXR Nuclear receptors are transcriptional regulators of dendritic cell chemotaxis Beceiro, Susana 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
title_short	LXR Nuclear receptors are transcriptional regulators of dendritic cell chemotaxis
title_full	LXR Nuclear receptors are transcriptional regulators of dendritic cell chemotaxis
title_fullStr	LXR Nuclear receptors are transcriptional regulators of dendritic cell chemotaxis
title_full_unstemmed	LXR Nuclear receptors are transcriptional regulators of dendritic cell chemotaxis
title_sort	LXR Nuclear receptors are transcriptional regulators of dendritic cell chemotaxis
dc.creator.none.fl_str_mv	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
author	Beceiro, Susana
author_facet	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
author_role	author
author2	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
author2_role	author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	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
topic	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
description	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.
publishDate	2018
dc.date.none.fl_str_mv	2018 2022 2022 2022
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion
format	article
status_str	acceptedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/189791
url	https://hdl.handle.net/2445/189791
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Versió postprint del document publicat a: https://doi.org/10.1128/MCB.00534-17 Molecular and Cellular Biology, 2018, vol. 38, num. 10, p. e00534-17 https://doi.org/10.1128/MCB.00534-17
dc.rights.none.fl_str_mv	(c) American Society for Microbiology, 2018 info:eu-repo/semantics/openAccess
rights_invalid_str_mv	(c) American Society for Microbiology, 2018
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	18 p. application/pdf
dc.publisher.none.fl_str_mv	American Society for Microbiology
publisher.none.fl_str_mv	American Society for Microbiology
dc.source.none.fl_str_mv	Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_	1869406318216871936
score	15.812429

LXR Nuclear receptors are transcriptional regulators of dendritic cell chemotaxis

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