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.
authors: Division 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.
authors: Qin
authors: Q
authors: Lan
authors: Xiaohui
authors: X
authors: Zhou
authors: Huimin
authors: H
authors: Fan
authors: Maogen
authors: M
authors: Chen
authors: Julie
authors: J
authors: Wang
authors: Bernhard
authors: B
authors: Ryffel
authors: David
authors: D
authors: Brand
authors: Rajalakshmy
authors: R
authors: Ramalingam
authors: Pawel R
authors: PR
authors: Kiela
authors: David A
authors: DA
authors: Horwitz
authors: Zhongmin
authors: Z
authors: Liu
authors: Song Guo
authors: SG
authors: Zheng
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D017346:Protein Serine-Threonine Kinases / Q000276:immunology; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology*
chemical_list: D017252:CD3 Complex; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II