Yang Ji, Li Qiao, Yang Xue, Li Ming
Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
Mol Med. 2015 Apr 15;21(1):364-70. doi: 10.2119/molmed.2014.00237.
Interleukin (IL)-9, which is produced mainly by CD4(+) T cells, is implicated in mast cell-related allergic diseases, although its involvement in systemic lupus erythematosus (SLE) pathogenesis remains unclear. Thus, we investigated the presence of IL-9 in lupus-prone MRL/Mp-lpr/lpr (MRL/lpr) mice and examined the role of IL-9 in lupus pathogenesis. Increased levels of IL-9(+) lymphocytes were detected in the spleens and kidneys of MRL/lpr mice and increased IL-9 levels in the spleen correlated with PNA(+) germinal center (GC) cell expansion. The percentage of CD4(+)IL-9(+) (Th9) cells was increased in MRL/lpr mice and serum IL-9 levels were elevated and closely related to the production of antibodies against double-stranded DNA (dsDNA). IL-9 appears to promote B-cell proliferation and immunoglobulin production, which could be blocked by inhibition of signal transducer and activator of transcription 3 (STAT3). Treatment with neutralizing anti-IL-9 antibody in vivo decreased serum anti-dsDNA-antibody titers and alleviated lupus nephritis in MRL/lpr mice. Our findings indicate expansion of Th9 cells in lupus-prone MRL/lpr mice and the correlation of IL-9 with B-cell proliferation and autoantibody production. These findings suggest that IL-9 is a potential therapeutic target for SLE.
白细胞介素（IL）-9主要由CD4(+) T细胞产生，与肥大细胞相关的过敏性疾病有关，但其在系统性红斑狼疮（SLE）发病机制中的作用尚不清楚。因此，我们研究了易患狼疮的MRL/Mp-lpr/lpr（MRL/lpr）小鼠中IL-9的存在情况，并探讨了IL-9在狼疮发病机制中的作用。在MRL/lpr小鼠的脾脏和肾脏中检测到IL-9(+)淋巴细胞水平升高，脾脏中IL-9水平的升高与PNA(+)生发中心（GC）细胞的扩增相关。MRL/lpr小鼠中CD4(+)IL-9(+)（Th9）细胞的百分比增加，血清IL-9水平升高，且与抗双链DNA（dsDNA）抗体的产生密切相关。IL-9似乎促进B细胞增殖和免疫球蛋白产生，这可通过抑制信号转导和转录激活因子3（STAT3）来阻断。体内用中和抗IL-9抗体治疗可降低MRL/lpr小鼠血清抗dsDNA抗体滴度，并减轻狼疮性肾炎。我们的研究结果表明，在易患狼疮的MRL/lpr小鼠中Th9细胞扩增，且IL-9与B细胞增殖和自身抗体产生相关。这些发现提示IL-9是SLE的一个潜在治疗靶点。
