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Mucosal administration of an altered CII263-272 peptide inhibits collagen-induced arthritis by suppression of Th1/Th17 cells and expansion of regulatory T cells
Zhao, Jinxia; Li, Ru; He, Jing; Shi, Jinxia; Long, Li; Li, Zhanguo
关键词Collagen Induced Arthritis Altered Peptide Arthritis Collagen Type Ii Rheumatoid Interleukin 17 Regulatory t Cells
刊名RHEUMATOLOGY INTERNATIONAL
2008-11-01
DOI10.1007/s00296-008-0634-4
29期:1页:9-16
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Rheumatology
研究领域[WOS]Rheumatology
关键词[WOS]RHEUMATOID-ARTHRITIS ; TRANSGENIC MICE ; II PEPTIDE ; TNF-ALPHA ; INTERLEUKIN-17 ; ANALOG ; PROTEIN ; EPITOPE ; LIGAND ; RAT
英文摘要

Rheumatoid arthritis (RA) is a systemic autoimmune disease mediated by T cells. Collagen type II (CII) is one of the autoantigens associated with RA. CII263-272 is a predominant CII antigenic peptide that can induce T-cell activation upon binding to MHC and interaction with the appropriate T-cell receptor (TCR). Altered CII263-272 peptides with substitution of specific amino acids could bind to RA-associated HLA-DR4/1 with no T cell stimulating effects and could inhibit T cell activation in RA. We performed this study to evaluate the effect of mucosal administration and to explore the mechanism of the inhibitory effect of altered CII263-272 peptide (267Q --> A, 270K --> A and 271G --> A) on collagen induced arthritis (CIA). CIA was induced in Lewis rats by immunization with bovine CII. Altered CII263-272 peptide was given intranasally beginning from arthritis onset. Wild CII263-272 peptide or PBS was administered as controls. Therapeutic effects were evaluated by arthritis scores, body weight change, and joint pathologic scores. The anti-CII antibody and its subtypes and the cytokines, IFN-gamma, IL-10, and IL-17 were measured with ELISA. Foxp3(+)CD4(+)CD25(+) regulatory T cell induction was assessed by FACS analysis. Following treatment with the altered CII263-272 peptide, arthiritis scores were reduced and body weight was increased. The altered CII263-272 peptide could retard the histologic lesion of the joints. The titers of anti-CII antibodies IgG2a in altered CII263-272 peptide treated rats decreased markedly compared to PBS-treated rats. The serum levels of IFN-gamma in rats treated with altered peptide was lower than that of rats treated with wild CII263-272 peptide and PBS. No differences were observed in the levels of serum IL-10 among the three groups. The altered CII263-272 peptide could decrease serum level of IL-17 and increase peripheral Foxp3(+)CD4(+)CD25(+) T cells at early stage of CIA. Mucosal administration of altered CII263-272 peptide could effectively inhibit the progression of CIA. Altered CII263-272 peptide could suppress Th17 cells and expand regulatory T cells in the early stage of the disease. The IgG2a subtype of anti-CII antibodies and IFN-gamma were reduced and in vivo Th1 responses were inhibited as a result of altered CII peptide treatment. Altered CII peptide is likely therapeutic in RA.

语种英语
WOS记录号WOS:000259698500002
项目编号30671933 ; 30430290
资助机构National Natural Science Foundation of China
引用统计
被引频次:27[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56417
专题北京大学第二临床医学院
北京大学第二临床医学院_风湿免疫科
北京大学第三临床医学院_风湿免疫科
作者单位Peking Univ, Sch Med, Dept Rheumatol & Immunol, Peoples Hosp, Beijing 100044, Peoples R China
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Zhao, Jinxia,Li, Ru,He, Jing,et al. Mucosal administration of an altered CII263-272 peptide inhibits collagen-induced arthritis by suppression of Th1/Th17 cells and expansion of regulatory T cells[J]. RHEUMATOLOGY INTERNATIONAL,2008,29(1):9-16.
APA Zhao, Jinxia,Li, Ru,He, Jing,Shi, Jinxia,Long, Li,&Li, Zhanguo.(2008).Mucosal administration of an altered CII263-272 peptide inhibits collagen-induced arthritis by suppression of Th1/Th17 cells and expansion of regulatory T cells.RHEUMATOLOGY INTERNATIONAL,29(1),9-16.
MLA Zhao, Jinxia,et al."Mucosal administration of an altered CII263-272 peptide inhibits collagen-induced arthritis by suppression of Th1/Th17 cells and expansion of regulatory T cells".RHEUMATOLOGY INTERNATIONAL 29.1(2008):9-16.
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