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

doi:10.1093/jmcb/mjs040

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

Department of Medicine

Research output: Contribution to journal › Article › peer-review

76 Scopus citations

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 language	English (US)
Pages (from-to)	409-419
Number of pages	11
Journal	Journal of Molecular Cell Biology
Volume	4
Issue number	6
DOIs	https://doi.org/10.1093/jmcb/mjs040
State	Published - Dec 2012

All Science Journal Classification (ASJC) codes

Molecular Biology
Genetics
Cell Biology

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10.1093/jmcb/mjs040

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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.",

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 = dec,

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",

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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.

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DO - 10.1093/jmcb/mjs040

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AN - SCOPUS:84868579788

SN - 1674-2788

VL - 4

SP - 409

EP - 419

JO - Journal of Molecular Cell Biology

JF - Journal of Molecular Cell Biology

IS - 6

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

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