A novel IgA/Delta-like 4/Notch axis induces immunosuppressive activity in human dendritic cells

Abstract

We aimed to study whether IgA or IgG could modulate dendritic cells through the Notch pathway. Blood myeloid DC were isolated from controls or patients with allergic rhinitis (sensitized to house dust mite, Dermatophagoides pteronyssinus, Der p) and assayed for Notch ligand, Delta-Like 4 (DLL4) expression and co-cultured with allogeneic CD4+ T cells. An upregulation of DLL4 was observed in IgA-treated, but not IgG-treated DCs. In co-culture of DCs and T cells, pulsing DCs with IgA downregulated IL-13, IL-5 and IFN-γ responses, but upregulated IL-10. The suppressive effect of IgA was mediated by DLL4 not by IL-10. In contrast, IL-10 was required for the inhibition by IgG-DCs. Altogether, IgA imprints myeloid DCs with suppressive effects on CD4+ T cell responses to Th2 and Th1 antigens through activation of DLL4/Notch pathway, whereas IgG does not induce DLL4 expression, its inhibitory effects mainly relying on IL-10.