title: An activation-induced IL-15 isoform is a natural antagonist for IL-15 function.
abstract: 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-15ΔE6, generated by alternative splicing events of activated immune cells, including macrophages and B cells. In vitro study showed that IL-15ΔE6 could antagonize IL-15-mediated T cell proliferation. The receptor binding assay revealed that IL-15ΔE6 could bind to IL-15Rα and interfere with the binding between IL-15 and IL-15Rα. Over-expression of IL-15ΔE6 in the murine EAE model ameliorated the EAE symptoms of the mice. The clinical scores were significantly lower in the mice expressing IL-15ΔE6 than the control mice and the mice expressing IL-15. The inflammation and demyelination of the EAE mice expressing IL-15ΔE6 were less severe than the control group. Furthermore, flow cytometry analysis demonstrated that IL-15ΔE6 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-15ΔE6 could be induced during immune activation and function as a negative feedback mechanism to dampen IL-15-mediated inflammatory events.
authors.affiliation: Institute of Blood and Marrow Transplantation, Cyrus Tang Hematology Center, Department of Hematology, Collaborative Innovation Center of Hematology, the First Affiliated Hospital of Soochow University, Suzhou 215006, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Institute of Blood and Marrow Transplantation, Cyrus Tang Hematology Center, Department of Hematology, Collaborative Innovation Center of Hematology, the First Affiliated Hospital of Soochow University, Suzhou 215006, P. R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Institute of Blood and Marrow Transplantation, Cyrus Tang Hematology Center, Department of Hematology, Collaborative Innovation Center of Hematology, the First Affiliated Hospital of Soochow University, Suzhou 215006, P. R. China.
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Blood and Marrow Transplantation, Cyrus Tang Hematology Center, Department of Hematology, Collaborative Innovation Center of Hematology, the First Affiliated Hospital of Soochow University, Suzhou 215006, P. R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Institute of Blood and Marrow Transplantation, Cyrus Tang Hematology Center, Department of Hematology, Collaborative Innovation Center of Hematology, the First Affiliated Hospital of Soochow University, Suzhou 215006, P. R. China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Lin
authors.affiliation: Institute of Blood and Marrow Transplantation, Cyrus Tang Hematology Center, Department of Hematology, Collaborative Innovation Center of Hematology, the First Affiliated Hospital of Soochow University, Suzhou 215006, P. R. China.
authors.forename: Yonghao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Blood and Marrow Transplantation, Cyrus Tang Hematology Center, Department of Hematology, Collaborative Innovation Center of Hematology, the First Affiliated Hospital of Soochow University, Suzhou 215006, P. R. China.|Immunology Programme, Life Sciences Institute and Department of Microbiology and Immunology, National University of Singapore, Singapore 117456, Singapore.
authors.forename: Yu
authors.initials: Y
authors.lastname: Mei
authors.affiliation: Immunology Programme, Life Sciences Institute and Department of Microbiology and Immunology, National University of Singapore, Singapore 117456, Singapore.
authors.forename: Dedy
authors.initials: D
authors.lastname: Sandikin
authors.affiliation: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, P. R. China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Sun
authors.affiliation: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, P. R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhuang
authors.affiliation: Immunology Programme, Life Sciences Institute and Department of Microbiology and Immunology, National University of Singapore, Singapore 117456, Singapore.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Liu
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D016466:CHO Cells; D049109:Cell Proliferation; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005091:Exons / Q000235:genetics; D018014:Gene Transfer Techniques; D057446:Hydrodynamics; D007249:Inflammation / Q000473:pathology; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism*; D053720:Interleukin-15 Receptor alpha Subunit / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D000067996:RAW 264.7 Cells; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology
chemical_list: D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit; D020033:Protein Isoforms