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学科主题: 基础医学
题名:
Elevated Expression of Transmembrane IL-15 in Immune Cells Correlates with the Development of Murine Lupus: a Potential Target for Immunotherapy Against SLE
作者: Bo, H.1,2; Wei, X. -Q.3; Dong, H.1; Zhang, Y.1; Lv, P.1; Liu, W.1; Koutoulaki, A.3; Gao, X. -M.1,2
刊名: SCANDINAVIAN JOURNAL OF IMMUNOLOGY
发表日期: 2009-02-01
DOI: 10.1111/j.1365-3083.2008.02197.x
卷: 69, 期:2, 页:119-129
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Immunology
研究领域[WOS]: Immunology
关键词[WOS]: RECEPTOR-ALPHA-CHAIN ; MEMBRANE-BOUND INTERLEUKIN-15 ; NECROSIS-FACTOR-ALPHA ; CD8(+) T-CELLS ; NATURAL-KILLER ; IN-VIVO ; RHEUMATOID-ARTHRITIS ; LYMPHOID HOMEOSTASIS ; BETA-CHAIN ; PROLIFERATION
英文摘要:

Presentation in trans by the Interleukin-15 receptor alpha chain (IL-15R alpha) has been suggested as the main mechanism for IL-15 anchoring to the cell surface, but it is also evident that IL-15 can exist as a transmembrane protein. We herein demonstrate that replacement of the first 41 residues of human IL-15 (hIL-15) with Ig kappa chain leader sequence resulted in secretion of most of the recombinant hIL-15 expressed in transfectant cells, thus identifying the transmembrane region of IL-15. A fusion protein (hIL-15R alpha-Fc) between the extracellular domain of hIL-15R alpha and the Fc fragment of IgG1 was prepared and shown to be able to bind with transmembrane IL-15 (tmIL-15). The level of tmIL-15 expression in macrophages, activated T cells and B cells from 6-month-old BXSB male mice, an animal model for systemic lupus erythematosus (SLE), was significantly increased compared with that from BXSB females or young males. In addition, hIL-15R alpha-Fc was able to block the T cell stimulating and anti-apoptotic effect of the tmIL-15-positive BXSB macrophages in vitro. Intravenous administration of hIL-15R alpha-Fc reduced the titre of autoantibodies against dsDNA and also proteinuria in aged BXSB males, implying that neutralization of IL-15 activity in vivo may be an effective way of treating SLE.

语种: 英语
所属项目编号: 2007CB512406 ; 2006AA02Z495
项目资助者: National Key Basic Research Programs ; National "863" Programs ; Arthritis Research Campaign
WOS记录号: WOS:000262694400006
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65163
Appears in Collections:基础医学院_免疫学系_期刊论文

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作者单位: 1.Minist Publ Hlth, Key Lab Immunol, Beijing, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Immunol, Beijing 100083, Peoples R China
3.Cardiff Univ, Sch Dent, Dept Dent Hlth & Biol Sci, Cardiff, Wales

Recommended Citation:
Bo, H.,Wei, X. -Q.,Dong, H.,et al. Elevated Expression of Transmembrane IL-15 in Immune Cells Correlates with the Development of Murine Lupus: a Potential Target for Immunotherapy Against SLE[J]. SCANDINAVIAN JOURNAL OF IMMUNOLOGY,2009,69(2):119-129.
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