| First Author | Rombouts M | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 1 | Pages | e0169608 |
| PubMed ID | 28060909 | Mgi Jnum | J:245996 |
| Mgi Id | MGI:5914089 | Doi | 10.1371/journal.pone.0169608 |
| Citation | Rombouts M, et al. (2017) Long-Term Depletion of Conventional Dendritic Cells Cannot Be Maintained in an Atherosclerotic Zbtb46-DTR Mouse Model. PLoS One 12(1):e0169608 |
| abstractText | 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. |
