Neutralization of IL-4 and IFN-γ Facilitates inducing TGF-β-induced CD4+Foxp3+ Regulatory Cells

It has been well recognized that TGF-β is able to induce CD4+CD25+Foxp3+ suppressor/regulatory T (iTreg) cells and IL-2 facilitates iTreg induction and expansion, however, only half of TGF-β-induced CD4+CD25+ cells express Foxp3 and remaining CD4+CD25+Foxp3- cells may represent effector cells. Wheth...

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Main Authors: Tao, Xiaojuan, Ma, Jilin, Zhang, Yonghua, Yu, Jianning, Cai, Long, Wang, Juhua, Zheng, Song Guo
Format: Online
Language:English
Published: Master Publishing Group 2008
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614670/
id pubmed-3614670
recordtype oai_dc
spelling pubmed-36146702013-05-01 Neutralization of IL-4 and IFN-γ Facilitates inducing TGF-β-induced CD4+Foxp3+ Regulatory Cells Tao, Xiaojuan Ma, Jilin Zhang, Yonghua Yu, Jianning Cai, Long Wang, Juhua Zheng, Song Guo Article It has been well recognized that TGF-β is able to induce CD4+CD25+Foxp3+ suppressor/regulatory T (iTreg) cells and IL-2 facilitates iTreg induction and expansion, however, only half of TGF-β-induced CD4+CD25+ cells express Foxp3 and remaining CD4+CD25+Foxp3- cells may represent effector cells. Whether other factor(s) can increase Foxp3 expression by CD4+CD25+ cells induced with TGF-β is still unclear. Here we show that addition of exogenous IFN-γ or IL-4 diminished the ability of TGF-β to induce Foxp3 expression and IL-2 failed to rescue this decreased Foxp3 expression. Conversely, neutralization of IFN-γ and IL-4 significantly enhanced the ability of TGF-β to induce Foxp3 and develop the suppressive activity, indicating that different cytokine profiles affect the differentiation of CD4+CD25+Foxp3+ subset induced by TGF-β. These results show that combination of antibodies against IFN-γ and IL-4 and TGF-β enhances the efficacy of generation and function of iTreg cells and may therefore provide a novel therapeutic strategy for the treatment of autoimmune and other chronic inflammatory diseases. Master Publishing Group 2008-03 /pmc/articles/PMC3614670/ /pubmed/23675066 Text en © Xiaojuan Tao et al. Licensee Master Publishing Group http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Tao, Xiaojuan
Ma, Jilin
Zhang, Yonghua
Yu, Jianning
Cai, Long
Wang, Juhua
Zheng, Song Guo
spellingShingle Tao, Xiaojuan
Ma, Jilin
Zhang, Yonghua
Yu, Jianning
Cai, Long
Wang, Juhua
Zheng, Song Guo
Neutralization of IL-4 and IFN-γ Facilitates inducing TGF-β-induced CD4+Foxp3+ Regulatory Cells
author_facet Tao, Xiaojuan
Ma, Jilin
Zhang, Yonghua
Yu, Jianning
Cai, Long
Wang, Juhua
Zheng, Song Guo
author_sort Tao, Xiaojuan
title Neutralization of IL-4 and IFN-γ Facilitates inducing TGF-β-induced CD4+Foxp3+ Regulatory Cells
title_short Neutralization of IL-4 and IFN-γ Facilitates inducing TGF-β-induced CD4+Foxp3+ Regulatory Cells
title_full Neutralization of IL-4 and IFN-γ Facilitates inducing TGF-β-induced CD4+Foxp3+ Regulatory Cells
title_fullStr Neutralization of IL-4 and IFN-γ Facilitates inducing TGF-β-induced CD4+Foxp3+ Regulatory Cells
title_full_unstemmed Neutralization of IL-4 and IFN-γ Facilitates inducing TGF-β-induced CD4+Foxp3+ Regulatory Cells
title_sort neutralization of il-4 and ifn-γ facilitates inducing tgf-β-induced cd4+foxp3+ regulatory cells
description It has been well recognized that TGF-β is able to induce CD4+CD25+Foxp3+ suppressor/regulatory T (iTreg) cells and IL-2 facilitates iTreg induction and expansion, however, only half of TGF-β-induced CD4+CD25+ cells express Foxp3 and remaining CD4+CD25+Foxp3- cells may represent effector cells. Whether other factor(s) can increase Foxp3 expression by CD4+CD25+ cells induced with TGF-β is still unclear. Here we show that addition of exogenous IFN-γ or IL-4 diminished the ability of TGF-β to induce Foxp3 expression and IL-2 failed to rescue this decreased Foxp3 expression. Conversely, neutralization of IFN-γ and IL-4 significantly enhanced the ability of TGF-β to induce Foxp3 and develop the suppressive activity, indicating that different cytokine profiles affect the differentiation of CD4+CD25+Foxp3+ subset induced by TGF-β. These results show that combination of antibodies against IFN-γ and IL-4 and TGF-β enhances the efficacy of generation and function of iTreg cells and may therefore provide a novel therapeutic strategy for the treatment of autoimmune and other chronic inflammatory diseases.
publisher Master Publishing Group
publishDate 2008
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614670/
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