Tolerogenic Splenic IDO+ Dendritic Cells from the Mice Treated with Induced-Treg Cells Suppress Collagen-Induced Arthritis

TGF-β-induced regulatory T cells (iTregs) retain Foxp3 expression and immune-suppressive activity in collagen-induced arthritis (CIA). However, the mechanisms whereby transferred iTregs suppress immune responses, particularly the interplay between iTregs and dendritic cells (DCs) in vivo, remain inc...

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Main Authors: Jie Yang, Yiming Yang, Huahua Fan, Hejian Zou
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2014/831054
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author Jie Yang
Yiming Yang
Huahua Fan
Hejian Zou
author_facet Jie Yang
Yiming Yang
Huahua Fan
Hejian Zou
author_sort Jie Yang
collection DOAJ
description TGF-β-induced regulatory T cells (iTregs) retain Foxp3 expression and immune-suppressive activity in collagen-induced arthritis (CIA). However, the mechanisms whereby transferred iTregs suppress immune responses, particularly the interplay between iTregs and dendritic cells (DCs) in vivo, remain incompletely understood. In this study, we found that after treatment with iTregs, splenic CD11c+DCs, termed “DCiTreg,” expressed tolerogenic phenotypes, secreted high levels of IL-10, TGF-β, and IDO, and showed potent immunosuppressive activity in vitro. After reinfusion with DCiTreg, marked antiarthritic activity improved clinical scores and histological end-points were observed. The serological levels of inflammatory cytokines and anti-CII antibodies were low and TGF-β production was high in the DCiTreg-treated group. DCiTreg also induced new iTregs in vivo. Moreover, the inhibitory activity of DCiTreg on CIA was lost following pretreatment with the inhibitor of indoleamine 2,3-dioxygenase (IDO). Collectively, these findings suggest that transferred iTregs could induce tolerogenic characteristics in splenic DCs and these cells could effectively dampen CIA in an IDO-dependent manner. Thus, the potential therapeutic effects of iTregs in CIA are likely maintained through the generation of tolerogenic DCs in vivo.
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series Journal of Immunology Research
spelling doaj-art-e419a0d5170c47079693218b6c3217692025-02-03T01:28:36ZengWileyJournal of Immunology Research2314-88612314-71562014-01-01201410.1155/2014/831054831054Tolerogenic Splenic IDO+ Dendritic Cells from the Mice Treated with Induced-Treg Cells Suppress Collagen-Induced ArthritisJie Yang0Yiming Yang1Huahua Fan2Hejian Zou3Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaBlood Engineering Laboratory, Shanghai Blood Center, Shanghai 200051, ChinaBlood Engineering Laboratory, Shanghai Blood Center, Shanghai 200051, ChinaDivision of Rheumatology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaTGF-β-induced regulatory T cells (iTregs) retain Foxp3 expression and immune-suppressive activity in collagen-induced arthritis (CIA). However, the mechanisms whereby transferred iTregs suppress immune responses, particularly the interplay between iTregs and dendritic cells (DCs) in vivo, remain incompletely understood. In this study, we found that after treatment with iTregs, splenic CD11c+DCs, termed “DCiTreg,” expressed tolerogenic phenotypes, secreted high levels of IL-10, TGF-β, and IDO, and showed potent immunosuppressive activity in vitro. After reinfusion with DCiTreg, marked antiarthritic activity improved clinical scores and histological end-points were observed. The serological levels of inflammatory cytokines and anti-CII antibodies were low and TGF-β production was high in the DCiTreg-treated group. DCiTreg also induced new iTregs in vivo. Moreover, the inhibitory activity of DCiTreg on CIA was lost following pretreatment with the inhibitor of indoleamine 2,3-dioxygenase (IDO). Collectively, these findings suggest that transferred iTregs could induce tolerogenic characteristics in splenic DCs and these cells could effectively dampen CIA in an IDO-dependent manner. Thus, the potential therapeutic effects of iTregs in CIA are likely maintained through the generation of tolerogenic DCs in vivo.http://dx.doi.org/10.1155/2014/831054
spellingShingle Jie Yang
Yiming Yang
Huahua Fan
Hejian Zou
Tolerogenic Splenic IDO+ Dendritic Cells from the Mice Treated with Induced-Treg Cells Suppress Collagen-Induced Arthritis
Journal of Immunology Research
title Tolerogenic Splenic IDO+ Dendritic Cells from the Mice Treated with Induced-Treg Cells Suppress Collagen-Induced Arthritis
title_full Tolerogenic Splenic IDO+ Dendritic Cells from the Mice Treated with Induced-Treg Cells Suppress Collagen-Induced Arthritis
title_fullStr Tolerogenic Splenic IDO+ Dendritic Cells from the Mice Treated with Induced-Treg Cells Suppress Collagen-Induced Arthritis
title_full_unstemmed Tolerogenic Splenic IDO+ Dendritic Cells from the Mice Treated with Induced-Treg Cells Suppress Collagen-Induced Arthritis
title_short Tolerogenic Splenic IDO+ Dendritic Cells from the Mice Treated with Induced-Treg Cells Suppress Collagen-Induced Arthritis
title_sort tolerogenic splenic ido dendritic cells from the mice treated with induced treg cells suppress collagen induced arthritis
url http://dx.doi.org/10.1155/2014/831054
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