title: Induced T regulatory cells suppress osteoclastogenesis and bone erosion in collagen-induced arthritis better than natural T regulatory cells.
abstract: BACKGROUND
  Although natural regulatory T cells (nTregs) can suppress osteoclastogenesis, the role of TGF-β-induced CD4+Foxp3+ Tregs (iTregs) in osteoclastogenesis remains unknown.
  
  
  OBJECTIVE
  To determine the effects of iTregs on osteoclastogenesis in vitro and on bone erosion in vivo in collagen-induced arthritis (CIA).
  
  
  METHODS
  Osteoclastogenesis was induced in bone marrow CD11b+ cells with receptor activator of nuclear factor κ B (NF-κB) ligand (RANKL) and macrophage colony stimulating factor. Graded doses of Tregs were added to inhibit osteoclastogenesis. Transwell and antibody blockade experiments were performed to assess the roles for cell contact and soluble cytokines. NF-κB activation was determined by western blot. iTregs or nTregs were adoptively transferred to mice with CIA to assess in vivo effects on disease incidence and bone erosion, the latter determined by CT scanning.
  
  
  RESULTS
  Both nTregs and iTregs greatly suppressed osteoclastogenesis in vitro, but only iTregs sustained this effect when interleukin-6 was present. iTregs, but not nTregs, significantly suppressed development of CIA. Bone erosions in iTregs-treated mice were diminished compared with untreated mice or nTregs-treated mice. Treatment with iTregs, but not with nTregs, dramatically decreased NF-κB p65/p50 levels in osteoclasts in vitro and p65/50 and RANKL expression by synovial tissues in vivo.
  
  
  CONCLUSIONS
  iTregs may be therapeutically beneficial in rheumatoid arthritis and related diseases associated with bone erosions.
authors: Division of Rheumatology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.|Division of Rheumatology, Huashan Hospital, Fudan University, Fudan, China.
authors: Ning
authors: N
authors: Kong
authors: Division of Rheumatology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.|Medicine Translation Center, Shanghai East Hospital, Tongji University, Shanghai, China.
authors: Qin
authors: Q
authors: Lan
authors: Division of Rheumatology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors: Wenru
authors: W
authors: Su
authors: Division of Rheumatology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors: Maogen
authors: M
authors: Chen
authors: Division of Rheumatology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors: Julie
authors: J
authors: Wang
authors: Arcadia High School, Los Angeles, California, USA.
authors: Ziyan
authors: Z
authors: Yang
authors: The Henry Samueli School of Engineering and Applied Science at UCLA, Los Angeles, California, USA.
authors: Ryan
authors: R
authors: Park
authors: The Henry Samueli School of Engineering and Applied Science at UCLA, Los Angeles, California, USA.
authors: Grant
authors: G
authors: Dagliyan
authors: The Henry Samueli School of Engineering and Applied Science at UCLA, Los Angeles, California, USA.
authors: Peter S
authors: PS
authors: Conti
authors: Research Service, VA Medical Center, Memphis, Tennessee, USA.
authors: David
authors: D
authors: Brand
authors: Medicine Translation Center, Shanghai East Hospital, Tongji University, Shanghai, China.
authors: Zhongmin
authors: Z
authors: Liu
authors: Division of Rheumatology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors: William
authors: W
authors: Stohl
authors: Division of Rheumatology, Huashan Hospital, Fudan University, Fudan, China.
authors: Hejian
authors: H
authors: Zou
authors: Division of Rheumatology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors: Song Guo
authors: SG
authors: Zheng
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D001862:Bone Resorption / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*