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Long-Term Depletion of Conventional Dendritic Cells Cannot Be Maintained in an Atherosclerotic Zbtb46-DTR Mouse Model

Rombouts, Miche ; Cools, Nathalie ; Grootaert, Mandy O J ; de Bakker, Flore ; Van Brussel, Ilse ; Wouters, An ; De Meyer, Guido R Y ; De Winter, Benedicte Y ; Schrijvers, Dorien M Lutgens, Esther

PloS one, 2017-01, Vol.12 (1), p.e0169608 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Long-Term Depletion of Conventional Dendritic Cells Cannot Be Maintained in an Atherosclerotic Zbtb46-DTR Mouse Model
Autor: Rombouts, Miche ; Cools, Nathalie ; Grootaert, Mandy O J ; de Bakker, Flore ; Van Brussel, Ilse ; Wouters, An ; De Meyer, Guido R Y ; De Winter, Benedicte Y ; Schrijvers, Dorien M
Lutgens, Esther
Assuntos: Animals ; Antibodies ; Antigens ; Arteriosclerosis ; Atherosclerosis ; Atherosclerosis - etiology ; Atherosclerosis - metabolism ; Atherosclerosis - pathology ; Biological markers ; Biology and Life Sciences ; Biomarkers ; Bone marrow ; Bone Marrow Transplantation ; Chimeras ; Dendritic cells ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Depletion ; Diphtheria ; Diphtheria toxin ; Diphtheria Toxin - immunology ; Diphtheria Toxin - pharmacology ; Disease Models, Animal ; Female ; Health sciences ; Homeostasis ; Inflammation ; Inflammatory diseases ; Irradiation ; Leukocyte Count ; Leukocytes - immunology ; Leukocytes - metabolism ; Low density lipoprotein receptors ; Male ; Medical laboratories ; Medical research ; Medicine ; Medicine and Health Sciences ; Mice ; Mice, Knockout ; Pharmaceuticals ; Plaque, Atherosclerotic - pathology ; Radiation ; Receptor density ; Receptors, LDL - deficiency ; Research and Analysis Methods ; Rodents ; Stem cell transplantation ; Transcription factors ; Transgenic animals ; Transgenic mice
É parte de: PloS one, 2017-01, Vol.12 (1), p.e0169608
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Conceptualization: MR NC IVB DS.Formal analysis: MR MG FdB.Funding acquisition: NC IVB BDW DS.Investigation: MR MG FdB DS.Methodology: MR NC MG IVB AW DS.Project administration: MR.Resources: NC AW GDM BDW DS.Supervision: MR NC DS.Validation: MR FdB DS.Visualization: MR.Writing – original draft: MR.Writing – review & editing: MR NC MG AW BDW DS.
Competing Interests: The authors have declared that no competing interests exist.
Descrição: 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. 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). 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. 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.
Editor: United States: Public Library of Science
Idioma: Inglês

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