Abstract

Dendritic cells (DCs) are professional antigen-presenting cells that play a key role in directing T-cell responses. Regulatory T (Treg) cells possess an immunosuppressive ability to inhibit effector T-cell responses, and Notch ligand Jagged1 (Jag1) is implicated in Treg cell differentiation. In this study, we evaluated whether bone marrow-derived DCs genetically engineered to express Jag1 (Jag1-DCs) would affect the maturation and function of DCs in vitro and further investigated the immunoregulatory ability of Jag1-DCs to manipulate T helper type 2 (Th2) -mediated allergic asthma in mice. We produced Jag1-DCs by adenoviral transduction. Overexpression of Jag1 by ovalbumin (OVA) -stimulated Jag1-DCs exhibited increased expression of programmed cell death ligand 1 (PD-L1) and OX40L molecules. Subsequently, co-culture of these OVA-pulsed Jag1-DCs with allogeneic or syngeneic CD4 + T cells promoted the generation of Foxp3 + Treg cells, and blocking PD-L1 using specific antibodies partially reduced Treg cell expansion. Furthermore, adoptive transfer of OVA-pulsed Jag1-DCs to mice with OVA-induced asthma reduced allergen-specific immunoglobulin E production, airway hyperresponsiveness, airway inflammation, and secretion of Th2-type cytokines (interleukin-4, interleukin-5, and interleukin-13). Notably, an increased number of Foxp3 + Treg cells associated with enhanced levels of transforming growth factor-β production was observed in Jag1-DC-treated mice. These data indicate that transgenic expression of Jag1 by DCs promotes induction of Foxp3 + Treg cells, which ameliorated Th2-mediated allergic asthma in mice. Our study supports an attractive strategy to artificially generate immunoregulatory DCs and provides a novel approach for manipulating Th2 cell-driven deleterious immune diseases.

Original languageEnglish
Pages (from-to)199-212
Number of pages14
JournalImmunology
Volume156
Issue number2
DOIs
Publication statusPublished - Feb 1 2019

Keywords

  • asthma
  • dendritic cell
  • Jagged1
  • regulatory T cell
  • T helper type 2
  • Asthma/genetics
  • Gene Expression
  • Adenoviridae
  • Transduction, Genetic
  • T-Lymphocytes, Regulatory/immunology
  • Th2 Cells/immunology
  • Animals
  • Cytokines/genetics
  • Jagged-1 Protein/genetics
  • Dendritic Cells/immunology
  • Mice
  • Mice, Inbred BALB C

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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