Overexpression of Notch ligand Delta-like-1 by dendritic cells enhances their immunoregulatory capacity and exerts antiallergic effects on Th2-mediated allergic asthma in mice

Publication date: Available online 14 October 2017
Source:Clinical Immunology
Author(s): Chen-Chen Lee, Chu-Lun Lin, Sy-Jye Leu, Yueh-Lun Lee
Dendritic cells (DCs) are professional antigen-presenting cells, and Notch ligand Delta-like-1 (DLL1) on DCs was implicated in type 1T helper (Th1) differentiation. In this study, we produced genetically engineered bone marrow-derived DCs that expressed DLL1 (DLL1-DCs) by adenoviral transduction. DLL1-DCs exerted a fully mature phenotype, and had positive effects on expression levels of interleukin (IL)-12 and costimulatory molecules. Coculture of allogeneic T cells with ovalbumin (OVA)-pulsed DLL1-DCs enhanced T cell proliferative responses and promoted Th1 cell differentiation. Furthermore, adoptive transfer of OVA-stimulated DLL1-DCs into asthmatic mice alleviated the cardinal features of allergic asthma, including immunoglobulin E (IgE) production, airway hyperresponsiveness (AHR), airway inflammation, and production of Th2-type cytokines. Notably, enhanced levels of the Th1-biased IgG2a response and interferon (IFN)-γ production were observed in these mice. Taken together, these data indicate that DLL1-DCs promoted Th1 cell development to alter the Th1/Th2 ratio and ameliorate Th2-mediated allergic asthma in mice.

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