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

doi:10.1038/srep25822

	An activation-induced IL-15 isoform is a natural antagonist for IL-15 function
	Zhao, Lei 1; Hu, Bo 1; Zhang, Yinsheng 1; Song, Yuan 1; Lin, Dandan 1; Liu, Yonghao 1; Mei, Yu 1,2,3; Sandikin, Dedy 2,3; Sun, Weiping4 ; Zhuang, Min4 ; Liu, Haiyan 2,3
	2016-05-11
发表期刊	SCIENTIFIC REPORTS
ISSN	2045-2322
卷号	6
发表状态	已发表
DOI	10.1038/srep25822
摘要	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.
收录类别	SCI
语种	英语
资助项目	Suzhou city[SWG0904]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000375615200001
出版者	NATURE PUBLISHING GROUP
WOS关键词	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
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1837
专题	生命科学与技术学院生命科学与技术学院_PI研究组_庄敏组生命科学与技术学院_博士生
通讯作者	Liu, Haiyan
作者单位	1.Soochow Univ, Affiliated Hosp 1, Collaborat Innovat Ctr Hematol,Dept Hematol, Inst Blood & Marrow Transplantat,Cyrus Tang Hemat, Suzhou 215006, Peoples R China 2.Natl Univ Singapore, Inst Life Sci, Program Immunol, Singapore 117456, Singapore 3.Natl Univ Singapore, Dept Microbiol & Immunol, Singapore 117456, Singapore 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Lei,Hu, Bo,Zhang, Yinsheng,et al. An activation-induced IL-15 isoform is a natural antagonist for IL-15 function[J]. SCIENTIFIC REPORTS,2016,6.
APA	Zhao, Lei.,Hu, Bo.,Zhang, Yinsheng.,Song, Yuan.,Lin, Dandan.,...&Liu, Haiyan.(2016).An activation-induced IL-15 isoform is a natural antagonist for IL-15 function.SCIENTIFIC REPORTS,6.
MLA	Zhao, Lei,et al."An activation-induced IL-15 isoform is a natural antagonist for IL-15 function".SCIENTIFIC REPORTS 6(2016).