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Elevated expression of transmembrane IL-15 in immune cells correlates with the development of murine lupus: A potential target for immunotherapy against SLE

Bo, H., Wei, Xiao-Qing, Dong, H., Zhang, Y., Lv, Hai-Peng, Liu, W., Koutoulaki, A. and Gao, X. M. 2009. Elevated expression of transmembrane IL-15 in immune cells correlates with the development of murine lupus: A potential target for immunotherapy against SLE. Scandinavian Journal of Immunology 69 (2) , pp. 119-129. 10.111/j.1365.3083.2008.02197.x

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Abstract

Presentation in trans by the Interleukin-15 receptor a chain (IL-15Ra) 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 Igj 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-15Ra-Fc) between the extracellular domain of hIL-15Ra 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-15Ra-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-15Ra-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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Publisher: Wiley
ISSN: 1365-3083
Last Modified: 04 Jun 2017 03:02
URI: http://orca.cf.ac.uk/id/eprint/15778

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