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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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Autores principales: Yang, Jie, Yang, Yiming, Fan, Huahua, Zou, Hejian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227353/
https://www.ncbi.nlm.nih.gov/pubmed/25405209
http://dx.doi.org/10.1155/2014/831054
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author Yang, Jie
Yang, Yiming
Fan, Huahua
Zou, Hejian
author_facet Yang, Jie
Yang, Yiming
Fan, Huahua
Zou, Hejian
author_sort Yang, Jie
collection PubMed
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 “DC(iTreg),” expressed tolerogenic phenotypes, secreted high levels of IL-10, TGF-β, and IDO, and showed potent immunosuppressive activity in vitro. After reinfusion with DC(iTreg), 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 DC(iTreg)-treated group. DC(iTreg) also induced new iTregs in vivo. Moreover, the inhibitory activity of DC(iTreg) 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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spelling pubmed-42273532014-11-17 Tolerogenic Splenic IDO(+) Dendritic Cells from the Mice Treated with Induced-Treg Cells Suppress Collagen-Induced Arthritis Yang, Jie Yang, Yiming Fan, Huahua Zou, Hejian J Immunol Res Research Article 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 “DC(iTreg),” expressed tolerogenic phenotypes, secreted high levels of IL-10, TGF-β, and IDO, and showed potent immunosuppressive activity in vitro. After reinfusion with DC(iTreg), 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 DC(iTreg)-treated group. DC(iTreg) also induced new iTregs in vivo. Moreover, the inhibitory activity of DC(iTreg) 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. Hindawi Publishing Corporation 2014 2014-10-27 /pmc/articles/PMC4227353/ /pubmed/25405209 http://dx.doi.org/10.1155/2014/831054 Text en Copyright © 2014 Jie Yang et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Yang, Jie
Yang, Yiming
Fan, Huahua
Zou, Hejian
Tolerogenic Splenic IDO(+) Dendritic Cells from the Mice Treated with Induced-Treg Cells Suppress Collagen-Induced Arthritis
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227353/
https://www.ncbi.nlm.nih.gov/pubmed/25405209
http://dx.doi.org/10.1155/2014/831054
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