Polyclonal CD4+Foxp3+ Treg cells induce TGFβ-dependent tolerogenic dendritic cells that suppress the murine lupus-like syndrome

Qin Lan, Xiaohui Zhou, Huimin Fan, Maogen Chen, Julie Wang, Bernhard Ryffel, David Brand, Rajalakshmy Ramalingam, Pawel R Kiela, David A. Horwitz, Zhongmin Liu, Song Guo Zheng

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Interplay between Foxp3+ regulatory T cells (Treg) and dendritic cells (DCs) maintains immunologic tolerance, but the effects of each cell on the other are not well understood. We report that polyclonal CD4 +Foxp3+ Treg cells induced ex vivo with transforming growth factor beta (TGFβ) (iTreg) suppress a lupus-like chronic graft-versus-host disease by preventing the expansion of immunogenic DCs and inducing protective DCs that generate additional recipient CD4 +Foxp3+ cells. The protective effects of the transferred iTreg cells required both interleukin (IL)-10 and TGFβ, but the tolerogenic effects of the iTreg on DCs, and the immunosuppressive effects of these DCs were exclusively TGFβ-dependent. The iTreg were unable to tolerize Tgfbr2-deficient DCs. These results support the essential role of DCs in 'infectious tolerance' and emphasize the central role of TGFβ in protective iTreg/DC interactions in vivo.

Original languageEnglish (US)
Pages (from-to)409-419
Number of pages11
JournalJournal of Molecular Cell Biology
Volume4
Issue number6
DOIs
StatePublished - Dec 2012

Fingerprint

Regulatory T-Lymphocytes
Transforming Growth Factor beta
Dendritic Cells
Central Tolerance
Graft vs Host Disease
Immunosuppressive Agents
Cell Communication
Interleukin-10

Keywords

  • dendritic cells
  • graft-versus-host disease
  • regulatory T cells
  • TGFβ

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Genetics

Cite this

Polyclonal CD4+Foxp3+ Treg cells induce TGFβ-dependent tolerogenic dendritic cells that suppress the murine lupus-like syndrome. / Lan, Qin; Zhou, Xiaohui; Fan, Huimin; Chen, Maogen; Wang, Julie; Ryffel, Bernhard; Brand, David; Ramalingam, Rajalakshmy; Kiela, Pawel R; Horwitz, David A.; Liu, Zhongmin; Zheng, Song Guo.

In: Journal of Molecular Cell Biology, Vol. 4, No. 6, 12.2012, p. 409-419.

Research output: Contribution to journalArticle

Lan, Q, Zhou, X, Fan, H, Chen, M, Wang, J, Ryffel, B, Brand, D, Ramalingam, R, Kiela, PR, Horwitz, DA, Liu, Z & Zheng, SG 2012, 'Polyclonal CD4+Foxp3+ Treg cells induce TGFβ-dependent tolerogenic dendritic cells that suppress the murine lupus-like syndrome', Journal of Molecular Cell Biology, vol. 4, no. 6, pp. 409-419. https://doi.org/10.1093/jmcb/mjs040
Lan, Qin ; Zhou, Xiaohui ; Fan, Huimin ; Chen, Maogen ; Wang, Julie ; Ryffel, Bernhard ; Brand, David ; Ramalingam, Rajalakshmy ; Kiela, Pawel R ; Horwitz, David A. ; Liu, Zhongmin ; Zheng, Song Guo. / Polyclonal CD4+Foxp3+ Treg cells induce TGFβ-dependent tolerogenic dendritic cells that suppress the murine lupus-like syndrome. In: Journal of Molecular Cell Biology. 2012 ; Vol. 4, No. 6. pp. 409-419.
@article{9d82a007b7f84e35bf146536d118f136,
title = "Polyclonal CD4+Foxp3+ Treg cells induce TGFβ-dependent tolerogenic dendritic cells that suppress the murine lupus-like syndrome",
abstract = "Interplay between Foxp3+ regulatory T cells (Treg) and dendritic cells (DCs) maintains immunologic tolerance, but the effects of each cell on the other are not well understood. We report that polyclonal CD4 +Foxp3+ Treg cells induced ex vivo with transforming growth factor beta (TGFβ) (iTreg) suppress a lupus-like chronic graft-versus-host disease by preventing the expansion of immunogenic DCs and inducing protective DCs that generate additional recipient CD4 +Foxp3+ cells. The protective effects of the transferred iTreg cells required both interleukin (IL)-10 and TGFβ, but the tolerogenic effects of the iTreg on DCs, and the immunosuppressive effects of these DCs were exclusively TGFβ-dependent. The iTreg were unable to tolerize Tgfbr2-deficient DCs. These results support the essential role of DCs in 'infectious tolerance' and emphasize the central role of TGFβ in protective iTreg/DC interactions in vivo.",
keywords = "dendritic cells, graft-versus-host disease, regulatory T cells, TGFβ",
author = "Qin Lan and Xiaohui Zhou and Huimin Fan and Maogen Chen and Julie Wang and Bernhard Ryffel and David Brand and Rajalakshmy Ramalingam and Kiela, {Pawel R} and Horwitz, {David A.} and Zhongmin Liu and Zheng, {Song Guo}",
year = "2012",
month = "12",
doi = "10.1093/jmcb/mjs040",
language = "English (US)",
volume = "4",
pages = "409--419",
journal = "Journal of Molecular Cell Biology",
issn = "1674-2788",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - Polyclonal CD4+Foxp3+ Treg cells induce TGFβ-dependent tolerogenic dendritic cells that suppress the murine lupus-like syndrome

AU - Lan, Qin

AU - Zhou, Xiaohui

AU - Fan, Huimin

AU - Chen, Maogen

AU - Wang, Julie

AU - Ryffel, Bernhard

AU - Brand, David

AU - Ramalingam, Rajalakshmy

AU - Kiela, Pawel R

AU - Horwitz, David A.

AU - Liu, Zhongmin

AU - Zheng, Song Guo

PY - 2012/12

Y1 - 2012/12

N2 - Interplay between Foxp3+ regulatory T cells (Treg) and dendritic cells (DCs) maintains immunologic tolerance, but the effects of each cell on the other are not well understood. We report that polyclonal CD4 +Foxp3+ Treg cells induced ex vivo with transforming growth factor beta (TGFβ) (iTreg) suppress a lupus-like chronic graft-versus-host disease by preventing the expansion of immunogenic DCs and inducing protective DCs that generate additional recipient CD4 +Foxp3+ cells. The protective effects of the transferred iTreg cells required both interleukin (IL)-10 and TGFβ, but the tolerogenic effects of the iTreg on DCs, and the immunosuppressive effects of these DCs were exclusively TGFβ-dependent. The iTreg were unable to tolerize Tgfbr2-deficient DCs. These results support the essential role of DCs in 'infectious tolerance' and emphasize the central role of TGFβ in protective iTreg/DC interactions in vivo.

AB - Interplay between Foxp3+ regulatory T cells (Treg) and dendritic cells (DCs) maintains immunologic tolerance, but the effects of each cell on the other are not well understood. We report that polyclonal CD4 +Foxp3+ Treg cells induced ex vivo with transforming growth factor beta (TGFβ) (iTreg) suppress a lupus-like chronic graft-versus-host disease by preventing the expansion of immunogenic DCs and inducing protective DCs that generate additional recipient CD4 +Foxp3+ cells. The protective effects of the transferred iTreg cells required both interleukin (IL)-10 and TGFβ, but the tolerogenic effects of the iTreg on DCs, and the immunosuppressive effects of these DCs were exclusively TGFβ-dependent. The iTreg were unable to tolerize Tgfbr2-deficient DCs. These results support the essential role of DCs in 'infectious tolerance' and emphasize the central role of TGFβ in protective iTreg/DC interactions in vivo.

KW - dendritic cells

KW - graft-versus-host disease

KW - regulatory T cells

KW - TGFβ

UR - http://www.scopus.com/inward/record.url?scp=84868579788&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868579788&partnerID=8YFLogxK

U2 - 10.1093/jmcb/mjs040

DO - 10.1093/jmcb/mjs040

M3 - Article

C2 - 22773728

AN - SCOPUS:84868579788

VL - 4

SP - 409

EP - 419

JO - Journal of Molecular Cell Biology

JF - Journal of Molecular Cell Biology

SN - 1674-2788

IS - 6

ER -