Ablation of Pericyte-Like Cells in Lungs by Oropharyngeal Aspiration of Diphtheria Toxin

We demonstrated previously that FoxD1-derived cells in the lung are enriched in pericyte-like cells in mouse lung. These cells express the common pericyte markers and are located adjacent to endothelial cells. In this study, we demonstrate the feasibility of administering diphtheria toxin (DT) by oropharyngeal aspiration as an approach to ablating FoxD1-derived cells. We crossed mice expressing Cre-recombinase under the FoxD1 promoter to Rosa26-loxP-STOP-loxP-iDTR mice and generated a bitransgenic line (FoxD1-Cre;Rs26-iDTR) in which FoxD1-derived cells heritably express simian or human diphtheria toxin receptor and are sensitive to DT. We delivered low-dose (0.5 ng/g) and high-dose (1ng/g × 2) to FoxD1-Cre;Rs26-iDTR mice and littermate control mice by oropharyngeal aspiration and evaluated ablation by flow cytometry and immunohistochemistry. FoxD1-Cre mice showed a 40–50% reduction in PDGFRβ+ cells by flow cytometry at Days 2 and 7 after DT administration, with a return of PDGFRβ+ cells at Day 28. Confoca...