Dataset Information


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

ABSTRACT: BACKGROUND AND AIMS: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.

SUBMITTER: Rombouts M 

PROVIDER: S-EPMC5218565 | BioStudies | 2017-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC3371733 | BioStudies
2015-01-01 | S-EPMC4272857 | BioStudies
2019-01-01 | S-EPMC7302510 | BioStudies
1000-01-01 | S-EPMC6077850 | BioStudies
1000-01-01 | S-EPMC5382263 | BioStudies
2019-01-01 | S-EPMC6286701 | BioStudies
2013-01-01 | S-EPMC3582120 | BioStudies
2017-01-01 | S-EPMC5526763 | BioStudies
2014-01-01 | S-EPMC4119831 | BioStudies
2012-01-01 | S-EPMC3529409 | BioStudies