PMID- 37172103
OWN - NLM
STAT- MEDLINE
DCOM- 20230515
LR  - 20230530
IS  - 2470-9468 (Electronic)
IS  - 2470-9468 (Linking)
VI  - 8
IP  - 83
DP  - 2023 May 12
TI  - LXR signaling controls homeostatic dendritic cell maturation.
PG  - eadd3955
LID - 10.1126/sciimmunol.add3955 [doi]
AB  - Dendritic cells (DCs) mature in an immunogenic or tolerogenic manner depending on 
      the context in which an antigen is perceived, preserving the balance between 
      immunity and tolerance. Whereas the pathways driving immunogenic maturation in 
      response to infectious insults are well-characterized, the signals that drive 
      tolerogenic maturation during homeostasis are still poorly understood. We found 
      that the engulfment of apoptotic cells triggered homeostatic maturation of type 1 
      conventional DCs (cDC1s) within the spleen. This maturation process could be 
      mimicked by engulfment of empty, nonadjuvanted lipid nanoparticles (LNPs), was 
      marked by intracellular accumulation of cholesterol, and was highly specific to 
      cDC1s. Engulfment of either apoptotic cells or cholesterol-rich LNPs led to the 
      activation of the liver X receptor (LXR) pathway, which promotes the efflux of 
      cellular cholesterol, and repressed genes associated with immunogenic maturation. 
      In contrast, simultaneous engagement of TLR3 to mimic viral infection via 
      administration of poly(I:C)-adjuvanted LNPs repressed the LXR pathway, thus 
      delaying cellular cholesterol efflux and inducing genes that promote T 
      cell-mediated immunity. These data demonstrate that conserved cellular 
      cholesterol efflux pathways are differentially regulated in tolerogenic versus 
      immunogenic cDC1s and suggest that administration of nonadjuvanted 
      cholesterol-rich LNPs may be an approach for inducing tolerogenic DC maturation.
FAU - Bosteels, Victor
AU  - Bosteels V
AUID- ORCID: 0000-0001-8838-021X
AD  - Laboratory for ER Stress and Inflammation, VIB-UGent Center for Inflammation 
      Research, Ghent, Belgium.
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
FAU - Marechal, Sandra
AU  - Marechal S
AUID- ORCID: 0000-0002-1275-3486
AD  - Laboratory for ER Stress and Inflammation, VIB-UGent Center for Inflammation 
      Research, Ghent, Belgium.
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
FAU - De Nolf, Clint
AU  - De Nolf C
AUID- ORCID: 0000-0002-2033-1830
AD  - Laboratory for ER Stress and Inflammation, VIB-UGent Center for Inflammation 
      Research, Ghent, Belgium.
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
AD  - Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
AD  - Barriers in Inflammation, VIB-UGent Center for Inflammation Research, Ghent, 
      Belgium.
FAU - Rennen, Sofie
AU  - Rennen S
AUID- ORCID: 0000-0002-2411-2045
AD  - Laboratory for ER Stress and Inflammation, VIB-UGent Center for Inflammation 
      Research, Ghent, Belgium.
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
FAU - Maelfait, Jonathan
AU  - Maelfait J
AUID- ORCID: 0000-0002-1476-0583
AD  - Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
AD  - Molecular Signaling and Cell Death, VIB-UGent Center for Inflammation Research, 
      Ghent, Belgium.
FAU - Tavernier, Simon J
AU  - Tavernier SJ
AUID- ORCID: 0000-0003-2514-5655
AD  - Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
AD  - Primary Immune Deficiency Research Lab, Department of Internal Medicine and 
      Pediatrics, Centre for Primary Immunodeficiency Ghent, Ghent University Hospital, 
      Ghent, Belgium.
AD  - Unit of Molecular Signal Transduction in Inflammation, VIB-UGent Center for 
      Inflammation Research, Ghent, Belgium.
FAU - Vetters, Jessica
AU  - Vetters J
AUID- ORCID: 0000-0001-5817-0086
AD  - Laboratory for ER Stress and Inflammation, VIB-UGent Center for Inflammation 
      Research, Ghent, Belgium.
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
FAU - Van De Velde, Evelien
AU  - Van De Velde E
AD  - Laboratory for ER Stress and Inflammation, VIB-UGent Center for Inflammation 
      Research, Ghent, Belgium.
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
FAU - Fayazpour, Farzaneh
AU  - Fayazpour F
AD  - Laboratory for ER Stress and Inflammation, VIB-UGent Center for Inflammation 
      Research, Ghent, Belgium.
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
FAU - Deswarte, Kim
AU  - Deswarte K
AUID- ORCID: 0000-0002-9761-6973
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
AD  - Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for 
      Inflammation Research, Ghent, Belgium.
FAU - Lamoot, Alexander
AU  - Lamoot A
AD  - Department of Pharmaceutics, Ghent University, Ghent, Belgium.
FAU - Van Duyse, Julie
AU  - Van Duyse J
AD  - Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
AD  - VIB Flow Core, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
FAU - Martens, Liesbet
AU  - Martens L
AUID- ORCID: 0000-0001-9180-7456
AD  - Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
AD  - Laboratory of Myeloid Cell Biology in Tissue Homeostasis and Regeneration, 
      VIB-UGent Center for Inflammation Research, Ghent, Belgium.
AD  - Laboratory of Myeloid Cell Biology in Tissue Damage and Inflammation, VIB-UGent 
      Center for Inflammation Research, Ghent, Belgium.
FAU - Bosteels, Cedric
AU  - Bosteels C
AUID- ORCID: 0000-0003-3230-0879
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
AD  - Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for 
      Inflammation Research, Ghent, Belgium.
FAU - Roelandt, Ria
AU  - Roelandt R
AUID- ORCID: 0000-0001-9936-7555
AD  - Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation 
      Research, Ghent, Belgium.
AD  - VIB Single Cell Core, VIB, Ghent-Leuven, Belgium.
FAU - Emmaneel, Annelies
AU  - Emmaneel A
AUID- ORCID: 0000-0003-4569-2330
AD  - Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation 
      Research, Ghent, Belgium.
AD  - Department of Applied Mathematics, Computer Science and Statistics, Ghent 
      University, Ghent, Belgium.
FAU - Van Gassen, Sofie
AU  - Van Gassen S
AUID- ORCID: 0000-0002-7119-5330
AD  - Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation 
      Research, Ghent, Belgium.
AD  - Department of Applied Mathematics, Computer Science and Statistics, Ghent 
      University, Ghent, Belgium.
FAU - Boon, Louis
AU  - Boon L
AUID- ORCID: 0000-0002-0937-9171
AD  - Polpharma Biologics, Utrecht, Netherlands.
FAU - Van Isterdael, Gert
AU  - Van Isterdael G
AUID- ORCID: 0000-0001-6626-1316
AD  - Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
AD  - VIB Flow Core, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
FAU - Guillas, Isabelle
AU  - Guillas I
AUID- ORCID: 0000-0002-6073-0529
AD  - Sorbonne Universite, Inserm, Institute of Cardiometabolism and Nutrition (ICAN), 
      UMR_S1166, Hopital de la Pitie, Paris F-75013, France.
FAU - Vandamme, Niels
AU  - Vandamme N
AUID- ORCID: 0000-0001-6582-0040
AD  - Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation 
      Research, Ghent, Belgium.
AD  - VIB Single Cell Core, VIB, Ghent-Leuven, Belgium.
FAU - Hoglinger, Doris
AU  - Hoglinger D
AD  - Heidelberg University Biochemistry Center, 69120 Heidelberg, Germany.
FAU - De Geest, Bruno G
AU  - De Geest BG
AD  - Department of Pharmaceutics, Ghent University, Ghent, Belgium.
FAU - Le Goff, Wilfried
AU  - Le Goff W
AUID- ORCID: 0000-0002-7611-9644
AD  - Sorbonne Universite, Inserm, Institute of Cardiometabolism and Nutrition (ICAN), 
      UMR_S1166, Hopital de la Pitie, Paris F-75013, France.
FAU - Saeys, Yvan
AU  - Saeys Y
AUID- ORCID: 0000-0002-0415-1506
AD  - Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation 
      Research, Ghent, Belgium.
AD  - Department of Applied Mathematics, Computer Science and Statistics, Ghent 
      University, Ghent, Belgium.
FAU - Ravichandran, Kodi S
AU  - Ravichandran KS
AUID- ORCID: 0000-0001-9049-1410
AD  - Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
AD  - Unit for Cell Clearance in Health and Disease, VIB-UGent Center for Inflammation 
      Research, Ghent, Belgium.
AD  - Center for Cell Clearance, Department of Microbiology, Immunology and Cancer 
      Biology, University of Virginia, Charlottesville, VA, USA.
FAU - Lambrecht, Bart N
AU  - Lambrecht BN
AUID- ORCID: 0000-0003-4376-6834
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
AD  - Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for 
      Inflammation Research, Ghent, Belgium.
AD  - Department of Pulmonary Medicine, Erasmus MC, Rotterdam, Netherlands.
FAU - Janssens, Sophie
AU  - Janssens S
AUID- ORCID: 0000-0003-1702-1636
AD  - Laboratory for ER Stress and Inflammation, VIB-UGent Center for Inflammation 
      Research, Ghent, Belgium.
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230512
PL  - United States
TA  - Sci Immunol
JT  - Science immunology
JID - 101688624
RN  - 0 (Liver X Receptors)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Liver X Receptors/metabolism
MH  - *Signal Transduction/genetics
MH  - Homeostasis
MH  - *Dendritic Cells
MH  - Cholesterol
EDAT- 2023/05/12 19:06
MHDA- 2023/05/15 06:42
CRDT- 2023/05/12 14:03
PHST- 2023/05/15 06:42 [medline]
PHST- 2023/05/12 19:06 [pubmed]
PHST- 2023/05/12 14:03 [entrez]
AID - 10.1126/sciimmunol.add3955 [doi]
PST - ppublish
SO  - Sci Immunol. 2023 May 12;8(83):eadd3955. doi: 10.1126/sciimmunol.add3955. Epub 
      2023 May 12.