| First Author | Vo T | Year | 2022 |
| Journal | Front Immunol | Volume | 13 |
| Pages | 1050494 | PubMed ID | 36578483 |
| Mgi Jnum | J:332693 | Mgi Id | MGI:7413408 |
| Doi | 10.3389/fimmu.2022.1050494 | Citation | Vo T, et al. (2022) Case report: Mafb promoter activity may define the alveolar macrophage dichotomy. Front Immunol 13:1050494 |
| abstractText | Cre-LoxP system has been widely used to induce recombination of floxed genes of interest. Currently available macrophage promoter-specific Cre recombinase mice strains have various limitations that warrants the testing of additional Cre strains. V-maf musculoaponeurotic fibrosarcoma oncogene family, protein b -Cre (Mafb-Cre) mice label macrophages in most organs such as spleen, small intestine, lung, bone marrow, and peritoneal cavity. However, whether Mafb-Cre recombinase targets the gene recombination in alveolar macrophage remains untested. Here, we utilized Mafb(Cre/WT)R26(mTmG/WT) strain that expresses mTOM protein in all the cells of mouse body except for those that express Mafb-Cre-regulated mEGFP. We performed fluorescent microscopy and flow cytometry to analyze mTOM and mEGFP expression in alveolar macrophages from Mafb(Cre/WT)R26(mTmG/WT) mice. Our analyses revealed that the Mafb-Cre is active in only ~40% of the alveolar macrophages in an age-independent manner. While Mafb- (mTOM+/mEGFP-) and Mafb+ (mEGFP+) alveolar macrophages exhibit comparable expression of CD11b and CD11c surface markers, the surface expression of MHCII is elevated in the Mafb+ (mEGFP+) macrophages. The bone marrow-derived macrophages from Mafb(Cre/WT)R26(mTmG/WT) mice are highly amenable to Cre-LoxP recombination in vitro. The bone marrow depletion and reconstitution experiment revealed that ~98% of alveolar macrophages from Mafb(Cre/WT)R26(mTmG/WT) --> WT chimera are amenable to the Mafb-Cre-mediated recombination. Finally, the Th2 stimulation and ozone exposure to the Mafb(Cre/WT)R26(mTmG/WT) mice promote the Mafb-Cre-mediated recombination in alveolar macrophages. In conclusion, while the Mafb-/Mafb+ dichotomy thwarts the use of Mafb-Cre for the induction of floxed alleles in the entire alveolar macrophage population, this strain provides a unique tool to induce gene deletion in alveolar macrophages that encounter Th2 microenvironment in the lung airspaces. |
