Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 48, Issue 5, Pages 861-873Publisher
WILEY
DOI: 10.1002/eji.201747351
Keywords
Allergic contact dermatitis (ACD); Diphtheria toxin receptor (DTR); Eosinophils; MCPT8; Neutrophils
Categories
Funding
- l'Agence Nationale de la Recherche [ANR-13-BSV1-0024-01, ANR-15-CE14-0009-03, ANR-17-CE14-0025-01]
- Freiburg Institute for Advanced Studies (FRIAS)
- University of Strasbourg Institute for Advanced Study (USIAS)
- Centre National de la Recherche Scientifique (CNRS)
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Universite de Strasbourg (UDS)
- University of Strasbourg
- Fondation pour la Recherche Medicale en France (FRM)
- Association pour la Recherche a l'IGBMC (ARI)
- Agence Nationale de la Recherche (ANR) [ANR-17-CE14-0025, ANR-15-CE14-0009, ANR-13-BSV1-0024] Funding Source: Agence Nationale de la Recherche (ANR)
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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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