title: Evaluation of the BDCA2-DTR Transgenic Mouse Model in Chronic and Acute Inflammation.
abstract: OBJECTIVE
  Plasmacytoid dendritic cells (pDCs) are a small subset of dendritic cells and the main producers of type I interferons. Besides their contribution to tolerance, they are known to be involved in autoimmune diseases and have recently been implicated in atherosclerosis. However, their precise involvement, particularly in advanced lesion development, remains elusive. Hence, we investigated the role of pDCs in atherogenesis vs atheroprogression by specifically depleting this cell population using the BDCA2-DTR mouse model bred to Apolipoprotein E (Apoe-/-) deficient mice.
  
  
  RESULTS
  Our results revealed that continuous diphtheria toxin-induced pDC depletion in Apoe-/- BDCA2-DTR mice receiving a high-fat diet (HFD) for 4 weeks did not alter lesion size or composition. Instead, these mice displayed increased B cell numbers and altered levels of inflammatory cytokines. Analysis of depletion efficiency showed that complete pDC depletion could only be sustained for one week and reoccurring pDCs sorted after 4 weeks did not express DTR anymore. Consequently, we analyzed lesion development in a model of partial carotid ligation, inducing established lesions after 5 weeks of HFD feeding, and only depleted pDCs during the last week of 5 weeks HFD feeding. Despite short-term, but efficient pDC depletion, we observed no differences in atherosclerotic lesion development, but changes in inflammatory cytokine titers. To assure the functionality of the BDCA2-DTR model in acute settings, we additionally examined the effect of pDC depletion in an indirect acute lung injury (iALI) model. This time, efficient pDC depletion resulted in a significantly reduced macrophage and neutrophil accumulation in the lung 12 hours after LPS challenge, underlining a pro-inflammatory role of pDCs in the innate immune response in iALI.
  
  
  CONCLUSIONS
  Taken together, the BDCA2-DTR mouse model only allows efficient pDC depletion for one week, which subsequently restricts its usability to more acute but not chronic inflammatory disease models.
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Mandl
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany; Academic Medical Center, Department of Pathology, Amsterdam University, Amsterdam, the Netherlands; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Maik
authors.initials: M
authors.lastname: Drechsler
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Jansen
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Carlos
authors.initials: C
authors.lastname: Neideck
authors.affiliation: Institute for Molecular Cardiovascular Research, RWTH Aachen University Aachen, Aachen, Germany.
authors.forename: Heidi
authors.initials: H
authors.lastname: Noels
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Faussner
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany; Academic Medical Center, Department of Pathology, Amsterdam University, Amsterdam, the Netherlands; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Soehnlein
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Döring
mesh_terms: D000208:Acute Disease; D055371:Acute Lung Injury / Q000473:pathology; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D002452:Cell Count; D002908:Chronic Disease; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D059305:Diet, High-Fat; D004167:Diphtheria Toxin / Q000276:immunology; D004195:Disease Models, Animal; D007249:Inflammation / Q000473:pathology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000187:drug effects / Q000473:pathology; D013154:Spleen / Q000473:pathology; D019076:Transgenes
chemical_list: D001057:Apolipoproteins E; D004167:Diphtheria Toxin; D008055:Lipids; D008070:Lipopolysaccharides; D017493:Leukocyte Common Antigens