Induced T regulatory cells suppress osteoclastogenesis and bone erosion in collagen-induced arthritis better than natural T regulatory cells

Ning Kong, Qin Lan, Maogen Chen, Tina Zheng, Wenru Su, Julie Wang, Ziyan Yang, Ryan Park, Grant Dagliyan, Peter S. Conti, David Brand, Zhongmin Liu, Hejian Zou, William Stohl, Song Guo Zheng

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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. Conclusion: iTregs may be therapeutically beneficial in rheumatoid arthritis and related diseases associated with bone erosions.

Original languageEnglish (US)
Pages (from-to)1567-1572
Number of pages6
JournalAnnals of the Rheumatic Diseases
Volume71
Issue number9
DOIs
StatePublished - Sep 1 2012

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Experimental Arthritis
Regulatory T-Lymphocytes
Osteogenesis
Erosion
Bone
Collagen
Bone and Bones
Macrophage Colony-Stimulating Factor
T-cells
Bone Diseases
Osteoclasts
Cytoplasmic and Nuclear Receptors
Interleukin-6
Bone Marrow Cells
Chemical activation
Rheumatoid Arthritis
Tissue
Cytokines
Ligands
Scanning

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Induced T regulatory cells suppress osteoclastogenesis and bone erosion in collagen-induced arthritis better than natural T regulatory cells. / Kong, Ning; Lan, Qin; Chen, Maogen; Zheng, Tina; Su, Wenru; Wang, Julie; Yang, Ziyan; Park, Ryan; Dagliyan, Grant; Conti, Peter S.; Brand, David; Liu, Zhongmin; Zou, Hejian; Stohl, William; Zheng, Song Guo.

In: Annals of the Rheumatic Diseases, Vol. 71, No. 9, 01.09.2012, p. 1567-1572.

Research output: Contribution to journalArticle

Kong, N, Lan, Q, Chen, M, Zheng, T, Su, W, Wang, J, Yang, Z, Park, R, Dagliyan, G, Conti, PS, Brand, D, Liu, Z, Zou, H, Stohl, W & Zheng, SG 2012, 'Induced T regulatory cells suppress osteoclastogenesis and bone erosion in collagen-induced arthritis better than natural T regulatory cells', Annals of the Rheumatic Diseases, vol. 71, no. 9, pp. 1567-1572. https://doi.org/10.1136/annrheumdis-2011-201052
Kong, Ning ; Lan, Qin ; Chen, Maogen ; Zheng, Tina ; Su, Wenru ; Wang, Julie ; Yang, Ziyan ; Park, Ryan ; Dagliyan, Grant ; Conti, Peter S. ; Brand, David ; Liu, Zhongmin ; Zou, Hejian ; Stohl, William ; Zheng, Song Guo. / Induced T regulatory cells suppress osteoclastogenesis and bone erosion in collagen-induced arthritis better than natural T regulatory cells. In: Annals of the Rheumatic Diseases. 2012 ; Vol. 71, No. 9. pp. 1567-1572.
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T1 - Induced T regulatory cells suppress osteoclastogenesis and bone erosion in collagen-induced arthritis better than natural T regulatory cells

AU - Kong, Ning

AU - Lan, Qin

AU - Chen, Maogen

AU - Zheng, Tina

AU - Su, Wenru

AU - Wang, Julie

AU - Yang, Ziyan

AU - Park, Ryan

AU - Dagliyan, Grant

AU - Conti, Peter S.

AU - Brand, David

AU - Liu, Zhongmin

AU - Zou, Hejian

AU - Stohl, William

AU - Zheng, Song Guo

PY - 2012/9/1

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N2 - 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. Conclusion: iTregs may be therapeutically beneficial in rheumatoid arthritis and related diseases associated with bone erosions.

AB - 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. Conclusion: iTregs may be therapeutically beneficial in rheumatoid arthritis and related diseases associated with bone erosions.

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