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Publication : Treatment of MCPT8<sup>DTR</sup> mice with high- or low-dose diphtheria toxin leads to differential depletion of basophils and granulocyte-macrophage progenitors.

First Author  El Hachem C Year  2018
Journal  Eur J Immunol Volume  48
Issue  5 Pages  861-873
PubMed ID  29315532 Mgi Jnum  J:263175
Mgi Id  MGI:6160723 Doi  10.1002/eji.201747351
Citation  El Hachem C, et al. (2018) Treatment of MCPT8(DTR) mice with high- or low-dose diphtheria toxin leads to differential depletion of basophils and granulocyte-macrophage progenitors. Eur J Immunol 48(5):861-873
abstractText  Basophils have been recently recognized to play important roles in type 2 immune responses during allergies and parasitic infection, largely due to the development of novel tools for the in vivo study of these cells. As such, the genetically-engineered MCPT8(DTR) mouse line has been used to specifically deplete basophils following treatment with diphtheria toxin (DT). In this study, we showed that DT-injected MCPT8(DTR) mice exhibited a striking decrease of eosinophils and neutrophils in skin when subjected to a hapten fluorescein isothiocyanate (FITC)-induced allergic contact dermatitis (ACD) experimental protocol. Unexpectedly, we found that loss of skin eosinophils and neutrophils was not due to a lack of basophil-mediated recruitment, as DT injection caused a systemic reduction of eosinophils and neutrophils in MCPT8(DTR) mice in a time-dependent manner. Furthermore, we found that hematopoietic stem-cell-derived granulocyte-macrophage progenitors (GMPs) expressed MCPT8 gene, and that these cells were depleted upon DT injection. Finally, we optimized a protocol in which a low-dose DT achieved a better specificity for depleting basophils, but not GMPs, in MCPT8(DTR) mice, and demonstrate that basophils do not play a major role in recruiting eosinophils and neutrophils to ACD skin. These data provide new and valuable information about functional studies of basophils.
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