2016年5月，我所刘海燕教授课题组在《Scientific Reports》上发表题为“Anactivation-induced IL-15 isoform is a natural antagonist for IL-15 function”，研究发现IL-15△E6亚型是在免疫激活中产生的，并且在免疫激活状态下抑制IL-15介导的炎性反应，发挥负向调控作用，从而维持机体的免疫稳态。

白介素15（IL-15）在免疫系统中发挥重要调节作用，在自身免疫疾病中异常高表达。其水平升高能够促进炎性细胞因子分泌，抑制T细胞激活后凋亡，促进CD8+记忆性T细胞存活而导致自身免疫病。

刘海燕教授课题组发现激活的免疫细胞包括巨噬细胞、B细胞能够通过选择性剪切产生一种缺失六号外显子的IL-15亚型IL-15△E6。体外细胞实验表明IL-15△E6能够抑制IL-15介导的促T细胞增殖功能。受体结合实验进一步显示IL-15△E6能够与IL-15Rα结合，该结合影响了IL-15和IL-15Rα之间的相互结合。在小鼠EAE模型中过表达IL-15△E6能够减轻小鼠的EAE临床症状，其临床评分与对照小鼠及过表达IL-15的小鼠相比显著降低。此外，流式细胞仪检测结果证明在小鼠EAE模型中IL-15△E6的表达能够显著降低小鼠脾脏和脊髓中炎性T细胞的百分比，抑制巨噬细胞在中枢神经系统中的浸润。

原文摘要：Interleukin 15(IL-15) expression induces the secretion of inflammatory cytokines, inhibitsthe apoptosis of activated T cells and prolongs the survival of CD8+ memory Tcells. Here we identified an IL-15 isoform lacking exon-6, IL-15ΔE6, generatedby alternative splicing events of activated immune cells, including macrophagesand B cells. In vitro study showed that IL-15ΔE6 could antagonizeIL-15-mediated T cell proliferation. The receptor binding assay revealed thatIL-15ΔE6 could bind to IL-15Rα and interfere with the binding between IL-15 andIL-15Rα. Over-expression of IL-15ΔE6 in the murine EAE model ameliorated the EAEsymptoms of the mice. The clinical scores were significantly lower in the miceexpressing IL-15ΔE6 than the control mice and the mice expressing IL-15. Theinflammation and demyelination of the EAE mice expressing IL-15ΔE6 were lesssevere than the control group. Furthermore, flow cytometry analysisdemonstrated that IL-15ΔE6 expression reduced the percentages of inflammatory Tcells in the spleen and spinal cord, and inhibited the infiltration ofmacrophages to the CNS. Our results demonstrated that IL-15ΔE6 could be inducedduring immune activation and function as a negative feedback mechanism todampen IL-15-mediated inflammatory events.