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

Scand J Immunol. 2009 Feb;69(2):119-29. doi: 10.1111/j.1365-3083.2008.02197.x.


Presentation in trans by the Interleukin-15 receptor alpha chain (IL-15Ralpha) 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 Igkappa 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-15Ralpha-Fc) between the extracellular domain of hIL-15Ralpha 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-15Ralpha-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-15Ralpha-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • COS Cells
  • Chlorocebus aethiops
  • Female
  • Humans
  • Immunoglobulin Fc Fragments / biosynthesis
  • Interleukin-15 / antagonists & inhibitors
  • Interleukin-15 / chemistry
  • Interleukin-15 / physiology*
  • Lupus Erythematosus, Systemic / etiology*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / therapy
  • Lymphocyte Activation
  • Macrophages / physiology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Receptors, Interleukin-15 / biosynthesis
  • Receptors, Interleukin-15 / therapeutic use
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / therapeutic use


  • Immunoglobulin Fc Fragments
  • Interleukin-15
  • Receptors, Interleukin-15
  • Recombinant Fusion Proteins