Treatment of MCPT8 mice with high- or low-dose diphtheria toxin leads to differential depletion of basophils and granulocyte-macrophage progenitors.

Fiche publication

Date publication

janvier 2018

Journal

European journal of immunology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr CHAN Susan , Dr LI Mei , Dr KIRSTETTER Peggy

Tous les auteurs :
El Hachem C, Hener P, Kirstetter P, Li J, Chan S, Li M

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/29315532

Résumé

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 mouse line has been used to specifically deplete basophils following treatment with diphtheria toxin (DT). In this study, we showed that DT-injected MCPT8 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 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 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.