Mechanisms Mediating Asthma Tolerance Induced By Regulatory Dendritic Cells Through CD4+CD25+Foxp3+ T Regulatory Cells
type: CreativeWork
description: IL-10-treated tolerogenic dendritic cells (DC10) have been used as a powerful tool for the treatment of experimental asthmatic responses. We explored the important role of CD4+CD25+Foxp3+ regulatory T cells (Treg) in the induction of tolerance by DC10 in three levels. We first used the siRNA approach to silence IL-10 gene expression in murine DC10 and we generated DC10 from CD80/86 or H-2Iab gene-KO mice. When used to treat asthmatic mice, the IL-10-silenced and MHCII-deficient DC10 had lost their abilities to induce tolerance, as determined by airway hyperresponsiveness (AHR), eosinophilia and Th2 responses, while the CD80-/-/86-/- DC10 had reduced tolerogenic activities. Further studies showed that the OVA-presenting DC10 up-regulated expression of the Treg-associated markers ICOS, PD-1, GITR, LAG-3 and CTLA-4 on pulmonary Treg cells in treated asthmatic mice while DC10 (CD80-/-CD86-/-), DC10 (Iab-/-) and DC10 (IL-10-/-) treatments lead to reduced Treg activation. This demonstrated that the activities of tolerogenic DCs are differentially affected by their expression of IL-10, MHC II and costimulatory molecules. DC10 induce allergen tolerance in asthmatic mice, during which the animals-lung Th2 T effector cells (Teff) are displaced by activated Treg cells. Intestinal DCs have been shown to promote oral tolerance by inducing antigen-naïve T cells to differentiate into Treg, but whether DCs can induce Teff to differentiate into Treg remains uncertain. We addressed this question in OVA-asthmatic mice that were treated with DC10. DC10 delivery maximally activated lung Treg in these animals at 3 wk post-treatment, as determined by in vitro and in vivo Treg-inhibitory assays. In parallel cultures OVA-, but not house dust mite (HDM)-, presenting DC10 induced ≈43% of CFSE-labeled CD25-/loFoxp3- Teff cells from asthmatic OVA-TCR transgenic mice to redifferentiate into Treg. We recapitulated this in vivo using OVA-asthmatic mice that were co-injected with OVA- or HDM-presen…
abstract: IL-10-treated tolerogenic dendritic cells (DC10) have been used as a powerful tool for the treatment of experimental asthmatic responses. We explored the important role of CD4+CD25+Foxp3+ regulatory T cells (Treg) in the induction of tolerance by DC10 in three levels. We first used the siRNA approach to silence IL-10 gene expression in murine DC10 and we generated DC10 from CD80/86 or H-2Iab gene-KO mice. When used to treat asthmatic mice, the IL-10-silenced and MHCII-deficient DC10 had lost their abilities to induce tolerance, as determined by airway hyperresponsiveness (AHR), eosinophilia and Th2 responses, while the CD80-/-/86-/- DC10 had reduced tolerogenic activities. Further studies showed that the OVA-presenting DC10 up-regulated expression of the Treg-associated markers ICOS, PD-1, GITR, LAG-3 and CTLA-4 on pulmonary Treg cells in treated asthmatic mice while DC10 (CD80-/-CD86-/-), DC10 (Iab-/-) and DC10 (IL-10-/-) treatments lead to reduced Treg activation. This demonstrated that the activities of tolerogenic DCs are differentially affected by their expression of IL-10, MHC II and costimulatory molecules. DC10 induce allergen tolerance in asthmatic mice, during which the animals-lung Th2 T effector cells (Teff) are displaced by activated Treg cells. Intestinal DCs have been shown to promote oral tolerance by inducing antigen-naïve T cells to differentiate into Treg, but whether DCs can induce Teff to differentiate into Treg remains uncertain. We addressed this question in OVA-asthmatic mice that were treated with DC10. DC10 delivery maximally activated lung Treg in these animals at 3 wk post-treatment, as determined by in vitro and in vivo Treg-inhibitory assays. In parallel cultures OVA-, but not house dust mite (HDM)-, presenting DC10 induced ≈43% of CFSE-labeled CD25-/loFoxp3- Teff cells from asthmatic OVA-TCR transgenic mice to redifferentiate into Treg. We recapitulated this in vivo using OVA-asthmatic mice that were co-injected with OVA- or HDM-presen…
author: Huang, Hui
language: eng
keywords: IL-10, regulatory dendritic cells, regulatory T cell, Tolerance, asthma
date published: 2012-10-05
date modified: 2026-07-24T04:27:20Z
provider: University of Saskatchewan
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Saskatchewan

PropertyValue
property ID: Handle
value: https://hdl.handle.net/10388/ETD-2012-09-682