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

50 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 languageEnglish (US)
Pages (from-to)409-419
Number of pages11
JournalJournal of Molecular Cell Biology
Volume4
Issue number6
DOIs
StatePublished - Dec 1 2012

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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    Lan, Q., Zhou, X., Fan, H., Chen, M., Wang, J., Ryffel, B., Brand, D., Ramalingam, R., Kiela, P. R., Horwitz, D. A., Liu, Z., & Zheng, S. G. (2012). Polyclonal CD4+Foxp3+ Treg cells induce TGFβ-dependent tolerogenic dendritic cells that suppress the murine lupus-like syndrome. Journal of Molecular Cell Biology, 4(6), 409-419. https://doi.org/10.1093/jmcb/mjs040