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
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.
Mots clés
Allergic contact dermatitis (ACD), Diphtheria toxin receptor (DTR), Eosinophils, MCPT8, Neutrophils
Référence
Eur. J. Immunol.. 2018 Jan 8;: