TY - JOUR
T1 - Activation of liver X receptor sensitizes human dendritic cells to inflammatory stimuli
AU - Töröcsik, Dániel
AU - Baráth, Mónika
AU - Benko, Szilvia
AU - Széles, Lajos
AU - Dezso, Balázs
AU - Póliska, Szilárd
AU - Hegyi, Zoltán
AU - Homolya, László
AU - Szatmári, István
AU - Lányi, Árpád
AU - Nagy, László
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/5/15
Y1 - 2010/5/15
N2 - Dendritic cells (DCs) respond to changes in their lipid environment by altering gene expression and immunophenotype. Some of these alterations are mediated via the nuclear receptor superfamily. However, little is known about the contribution of liver X receptor (LXR) to DC biology. In this study, we present a systematic analysis of LXR, activated by synthetic ligands or naturally occurring oxysterols in developing human monocyte-derived DCs.We found that LXRs are present and can be activated throughout DC differentiation in monocyte- and blood-derived DCs. Administration of LXR-specific natural or synthetic activators induced target gene expression accompanied by increased expression of DC maturation markers, such as CD80 and CD86. In mature DCs, LXR activation augmented the production of inflammatory cytokines IL-12, TNF-α, IL-6, and IL-8 and resulted in an increased capacity to activate CD4+ T cell proliferation upon ligation with TLR4 or TLR3 ligands. These effects appear to be underpinned by prolonged NF-κB signaling. Supporting such an inflammatory role, we found that LXR positive DCs are present in reactive lymph nodes in vivo. We propose that activation of LXR represents a novel lipid-signaling paradigm that alters the inflammatory response of human DCs.
AB - Dendritic cells (DCs) respond to changes in their lipid environment by altering gene expression and immunophenotype. Some of these alterations are mediated via the nuclear receptor superfamily. However, little is known about the contribution of liver X receptor (LXR) to DC biology. In this study, we present a systematic analysis of LXR, activated by synthetic ligands or naturally occurring oxysterols in developing human monocyte-derived DCs.We found that LXRs are present and can be activated throughout DC differentiation in monocyte- and blood-derived DCs. Administration of LXR-specific natural or synthetic activators induced target gene expression accompanied by increased expression of DC maturation markers, such as CD80 and CD86. In mature DCs, LXR activation augmented the production of inflammatory cytokines IL-12, TNF-α, IL-6, and IL-8 and resulted in an increased capacity to activate CD4+ T cell proliferation upon ligation with TLR4 or TLR3 ligands. These effects appear to be underpinned by prolonged NF-κB signaling. Supporting such an inflammatory role, we found that LXR positive DCs are present in reactive lymph nodes in vivo. We propose that activation of LXR represents a novel lipid-signaling paradigm that alters the inflammatory response of human DCs.
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U2 - 10.4049/jimmunol.0902399
DO - 10.4049/jimmunol.0902399
M3 - Article
C2 - 20410489
AN - SCOPUS:77954697899
SN - 0022-1767
VL - 184
SP - 5456
EP - 5465
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -