title: Long-Term Depletion of Conventional Dendritic Cells Cannot Be Maintained in an Atherosclerotic Zbtb46-DTR Mouse Model.
abstract: OBJECTIVE
  Increased evidence suggests a pro-atherogenic role for conventional dendritic cells (cDC). However, due to the lack of an exclusive marker for cDC, their exact contribution to atherosclerosis remains elusive. Recently, a unique transcription factor was described for cDC, namely Zbtb46, enabling us to selectively target this cell type in mice.
  
  
  METHODS
  Low-density lipoprotein receptor-deficient (Ldlr-/-) mice were transplanted with bone marrow from Zbtb46-diphtheria toxin receptor (DTR) transgenic mice following total body irradiation. Zbtb46-DTR→Ldlr-/- chimeras were fed a Western-type diet for 18 weeks while cDC were depleted by administering diphtheria toxin (DT).
  
  
  RESULTS
  Although we confirmed efficient direct induction of cDC death in vitro and in vivo upon DT treatment of Zbtb46-DTR mice, advanced atherosclerotic plaque size and composition was not altered. Surprisingly, however, analysis of Zbtb46-DTR→Ldlr-/- chimeras showed that depletion of cDC was not sustained following 18 weeks of DT treatment. In contrast, high levels of anti-DT antibodies were detected.
  
  
  CONCLUSIONS
  Because of the observed generation of anti-DT antibodies and consequently the partial depletion of cDC, no clear decision can be taken on the role of cDC in atherosclerosis. Our results underline the unsuitability of Zbtb46-DTR→Ldlr-/- mice for studying the involvement of cDC in maintaining the disease process of atherosclerosis, as well as of other chronic inflammatory diseases.
authors.affiliation: Laboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Miche
authors.identifier: http://orcid.org/0000-0003-1106-7035
authors.initials: M
authors.lastname: Rombouts
authors.affiliation: Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (Vaxinfectio), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cools
authors.affiliation: Laboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Mandy O J
authors.initials: MO
authors.lastname: Grootaert
authors.affiliation: Laboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Flore
authors.initials: F
authors.lastname: de Bakker
authors.affiliation: Laboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Van Brussel
authors.affiliation: Center for Oncological Research, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Wouters
authors.affiliation: Laboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Guido R Y
authors.initials: GR
authors.lastname: De Meyer
authors.affiliation: Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Benedicte Y
authors.initials: BY
authors.lastname: De Winter
authors.affiliation: Laboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Dorien M
authors.initials: DM
authors.lastname: Schrijvers
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers; D016026:Bone Marrow Transplantation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004167:Diphtheria Toxin / Q000276:immunology / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000473:pathology; D011973:Receptors, LDL / Q000172:deficiency
chemical_list: D015415:Biomarkers; D004167:Diphtheria Toxin; D011973:Receptors, LDL