Journal of Allergy and Clinical Immunology
The Notch Mediator RBP-J in CD4 T Cells Plays a Crucial Role in the Induction of Allergic Asthma in Mice
Section snippets
Rationale
The role of the Jagged-Notch signaling pathway was studied in a house dust mite (HDM) model for asthma and in the context of DC-T-cell interaction. Jagged-Notch signaling is known to control IL-4-independent differentiation of Th2 cells, through direct transcriptional induction of the Gata3 gene. RBP-J is the main effector of Notch and is required for IL-4-independent Th2 cell differentiation. Here we used T lymphocyte-specific deletion of the RBP-J gene to investigate whether RBP-J plays a
Methods
Conditional RBP-J KO (CD4-Cre loxP-flanked Rbp-j alleles) and WT littermates were studied in a HDM asthma model or by sensitization and challenge with GM-CSF-cultured bone marrow-derived dendritic cells (DCs). Bronchial-hyperreactivity (flexivent) was examined and airway inflammation (eosinophils and T-cells producing IL-4, IL-5, IL-13, IFN-gamma and IL-17) was quantified in bronchial alveolar lavage. Serum IgE was measured by Elisa and Notch-ligand expression on DCs was confirmed by
Results
In the HDM-treated groups, WT animals developed asthma signs. In contrast, RBP-J KO animals failed to develop any signs of bronchial-hyperreactivity or eosinophilic inflammation. Neither serum IgE, Th2- nor Th1-cytokines were induced in RBP-J KO animals. On the other hand, IL-17 producing T-cells were induced in HDM-treated KO animals, showing that deficiency for RBP-J did not abrogate activation of CD4+T cells in general. Sensitisation and challenge with cultured DC, which expressed the
Conclusions
These findings show that Jagged-Notch signaling is required for the induction of asthma in mice.