An activation-induced IL-15 isoform is a natural antagonist for IL-15 function

作者：Zhao, Lei; Hu, Bo; Zhang, Yinsheng; Song, Yuan; Lin, Dandan; Liu, Yonghao; Mei, Yu; Sandikin, Dedy; Sun, Weiping; Zhuang, Min; Liu, Haiyan^*

来源：Scientific Reports, 2016, 6(1): 25822.

DOI：10.1038/srep25822

• EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
• REMITTING MULTIPLE-SCLEROSIS
• ALTERNATIVE SPLICE VARIANTS
• CELL GROWTH-FACTOR
• NF-KAPPA-B
• T-CELLS
• TRANSCRIPTIONAL ACTIVATION
• INDUCED ARTHRITIS
• INTERFERON-GAMMA
• HUMAN MONOCYTES

Interleukin 15 (IL-15) expression induces the secretion of inflammatory cytokines, inhibits the apoptosis of activated T cells and prolongs the survival of CD8(+) memory T cells. Here we identified an IL-15 isoform lacking exon-6, IL-15 Delta E6, generated by alternative splicing events of activated immune cells, including macrophages and B cells. In vitro study showed that IL-15 Delta E6 could antagonize IL-15-mediated T cell proliferation. The receptor binding assay revealed that IL-15 Delta E6 could bind to IL-15R alpha and interfere with the binding between IL-15 and IL-15Ra. Over-expression of IL-15 Delta E6 in the murine EAE model ameliorated the EAE symptoms of the mice. The clinical scores were significantly lower in the mice expressing IL-15 Delta E6 than the control mice and the mice expressing IL-15. The inflammation and demyelination of the EAE mice expressing IL-15 Delta E6 were less severe than the control group. Furthermore, flow cytometry analysis demonstrated that IL-15 Delta E6 expression reduced the percentages of inflammatory T cells in the spleen and spinal cord, and inhibited the infiltration of macrophages to the CNS. Our results demonstrated that IL-15 Delta E6 could be induced during immune activation and function as a negative feedback mechanism to dampen IL-15-mediated inflammatory events.

• 出版日期2016-5-11
• 单位上海科技大学; 苏州大学