IL-9 signaling affects central nervous system resident cells during inflammatory stimuli.
IL-9 signaling affects central nervous system resident cells during inflammatory stimuli.
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DOI：
10.1016/j.yexmp.2015.07.010
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发表时间：
2015-12
影响因子：
3.6
通讯作者：
Rostami A
中科院分区：
文献类型：
--
作者：
Ding X;Cao F;Cui L;Ciric B;Zhang GX;Rostami A
白细胞介素 (IL) 9 是 Th9 细胞中的主要细胞因子，已被证明通过增强 T 细胞活化和分化，在实验性自身免疫性脑脊髓炎 (EAE)（一种多发性硬化症 (MS) 动物模型）中发挥致病作用；然而，IL-9 信号传导是否影响中枢神经系统 (CNS) 自身免疫期间的驻留细胞仍不清楚。在本研究中，我们发现IL-9受体（IL-9R）在星形胶质细胞、少突胶质祖细胞（OPC）、少突胶质细胞和小胶质细胞中高表达，并且在EAE期间其在脑和脊髓中的表达显着上调。此外，IL-9 增加了原代星形胶质细胞中趋化因子的表达，包括 CXCL9、CCL20 和 MMP3。尽管IL-9对小胶质细胞的增殖没有影响，但与其他促炎细胞因子结合时，它会降低OPC的增殖和分化，但与IFN-γ结合时则不会。 IL-9加IFN-γ促进OPC增殖和分化。这些发现表明 CNS 限制性 IL-9 信号传导可能参与 MS/EAE 的发病机制，从而通过破坏 CNS 细胞特异性 IL-9 信号传导为未来 MS/EAE 治疗提供潜在的治疗靶点。
Interleukin (IL) 9, a dominant cytokine in Th9 cells, has been proven to play a pathogenic role in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), by augmenting T cell activation and differentiation; however, whether IL-9 signaling affects central nervous system (CNS)-resident cells during CNS autoimmunity remains unknown. In the present study, we found that the IL-9 receptor (IL-9R) was highly expressed in astrocytes, oligodendrocyte progenitor cells (OPCs), oligodendrocytes and microglia cells, and that its expression was significantly upregulated in brain and spinal cord during EAE. In addition, IL-9 increased chemokine expression, including CXCL9, CCL20 and MMP3, in primary astrocytes. Although IL-9 had no effect on the proliferation of microglia cells, it decreased OPC proliferation and differentiation when in combination with other pro-inflammatory cytokines, but not with IFN-γ. IL-9 plus IFN-γ promoted OPC proliferation and differentiation. These findings indicate that CNS-restricted IL-9 signaling may be involved in the pathogenesis of MS/EAE, thus providing a potential therapeutic target for future MS/EAE treatment through disruption of CNS cell-specific IL-9 signaling.
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影响因子：
4.8
作者：
Chang SH;Dong C
通讯作者：
Dong C
影响因子：
32.4
作者：
Kang Z;Altuntas CZ;Gulen MF;Liu C;Giltiay N;Qin H;Liu L;Qian W;Ransohoff RM;Bergmann C;Stohlman S;Tuohy VK;Li X
通讯作者：
Li X
DOI：
10.1038/nri2848
发表时间：
2010-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.1303321
发表时间：
2015-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ding X;Yan Y;Li X;Li K;Ciric B;Yang J;Zhang Y;Wu S;Xu H;Chen W;Lovett-Racke AE;Zhang GX;Rostami A
通讯作者：
Rostami A
影响因子：
30.5
作者：
Dardalhon, Valerie;Awasthi, Amit;Kwon, Hyoung;Galileos, George;Gao, Wenda;Sobel, Raymond A.;Mitsdoerffer, Meike;Strom, Terry B.;Elyaman, Wassim;Ho, I-Cheng;Khoury, Samia;Oukka, Mohamed;Kuchroo, Vijay K.
通讯作者：
Kuchroo, Vijay K.