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Polyclonal CD4+Foxp3+ Treg cells induce TGFβ-dependent tolerogenic dendritic cells that suppress the murine lupus-like syndrome Free
Qin Lan1,2, Xiaohui Zhou1,2, Huimin Fan2, Maogen Chen1, Julie Wang1, Bernhard Ryffel3, David Brand4, Rajalakshmy Ramalingam5, Pawel R. Kiela5, David A. Horwitz1, Zhongmin Liu2,*, and Song Guo Zheng1,2,*
1Division of Rheumatology and Immunology, Department of Medicine, Keck School of Medicine at University of Southern California, 2011 Zonal Avenue, HMR710, Los Angeles, CA 90033, USA
2Institute of Immune and Transplantation, Shanghai East Hospital, Tongji University, Shanghai 200120, China
3University of Orléans and Molecular Immunology and Embryology, CNRS UMR6218, Orleans, France
4Research Service, Veterans Affairs Medical Center, Memphis, TN 38104, USA
5Departments of Pediatrics and Immunobiology, University of Arizona, Tucson, AZ 85721, USA *Correspondence to:Song Guo Zheng, E-mail: szheng@usc.edu; Zhongmin Liu, E-mail: zhongmin_liu@sina.com
J Mol Cell Biol, Volume 4, Issue 6, December 2012, 409-419,  https://doi.org/10.1093/jmcb/mjs040
Keyword: regulatory T cells, dendritic cells, TGFβ, graft-versus-host disease
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.

Volume 4, Issue 6
December 2012