IFN-γ signaling to astrocytes protects from autoimmune mediated neurological disability.
IFN-γ signaling to astrocytes protects from autoimmune mediated neurological disability.
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DOI：
10.1371/journal.pone.0042088
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Stohlman SA
中科院分区：
文献类型：
--
作者：
Hindinger C;Bergmann CC;Hinton DR;Phares TW;Parra GI;Hussain S;Savarin C;Atkinson RD;Stohlman SA
脱髓鞘和轴突变性是多发性硬化症(MS)患者进行性神经功能障碍的决定因素。居住在中枢神经系统(CNS)内的细胞是自身免疫性疾病发生、发展和随后控制的积极参与者；然而，它们的个体贡献还不是很清楚。星形胶质细胞是最丰富的中枢神经系统细胞类型，对环境信号高度敏感，在自身免疫脱髓鞘过程中既涉及有害结果，也涉及保护性结果。为了探讨炎症对星形胶质细胞活性的影响，建立了表达干扰素γ受体缺陷的转基因小鼠的实验性自身免疫性脑脊髓炎模型。抑制星形胶质细胞的干扰素-γ信号并不影响疾病的发生率、发病、症状的初始进展、血脑屏障的完整性或急性中枢神经系统炎症反应的组成。然而，在缺乏干扰素-γ信号的急性疾病高峰期脱髓鞘增加与持续的临床症状相关。疾病高峰后，临床缓解减轻、死亡率增加以及灰质内星形胶质细胞的持续激活表明，干扰素-γ信号转导星形胶质细胞在神经保护中起着关键作用。疾病缓解程度的降低与脱髓鞘、轴突变性和持续性炎症有关。中枢神经系统浸润的白细胞组成没有改变，但IL-10和IL-27的降低与疾病的持续有关。这些数据表明，星形胶质细胞在限制中枢神经系统自身免疫性疾病方面发挥了关键作用，这依赖于干扰素-γ受体参与介导的神经保护信号通路。
Demyelination and axonal degeneration are determinants of progressive neurological disability in patients with multiple sclerosis (MS). Cells resident within the central nervous system (CNS) are active participants in development, progression and subsequent control of autoimmune disease; however, their individual contributions are not well understood. Astrocytes, the most abundant CNS cell type, are highly sensitive to environmental cues and are implicated in both detrimental and protective outcomes during autoimmune demyelination. Experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice expressing signaling defective dominant-negative interferon gamma (IFN-γ) receptors on astrocytes to determine the influence of inflammation on astrocyte activity. Inhibition of IFN-γ signaling to astrocytes did not influence disease incidence, onset, initial progression of symptoms, blood brain barrier (BBB) integrity or the composition of the acute CNS inflammatory response. Nevertheless, increased demyelination at peak acute disease in the absence of IFN-γ signaling to astrocytes correlated with sustained clinical symptoms. Following peak disease, diminished clinical remission, increased mortality and sustained astrocyte activation within the gray matter demonstrate a critical role of IFN-γ signaling to astrocytes in neuroprotection. Diminished disease remission was associated with escalating demyelination, axonal degeneration and sustained inflammation. The CNS infiltrating leukocyte composition was not altered; however, decreased IL-10 and IL-27 correlated with sustained disease. These data indicate that astrocytes play a critical role in limiting CNS autoimmune disease dependent upon a neuroprotective signaling pathway mediated by engagement of IFN-γ receptors.
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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
影响因子：
3.5
作者：
BECK, J;RONDOT, P;WIETZERBIN, J
通讯作者：
WIETZERBIN, J
影响因子：
4.4
作者：
Fitzgerald, Denise C.;Ciric, Bogoljub;Rostami, Abdolmohamad
通讯作者：
Rostami, Abdolmohamad
DOI：
10.4049/jimmunol.0802954
发表时间：
2009-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Brambilla R;Persaud T;Hu X;Karmally S;Shestopalov VI;Dvoriantchikova G;Ivanov D;Nathanson L;Barnum SR;Bethea JR
通讯作者：
Bethea JR
影响因子：
6.2
作者：
Hamo, Ludwig;Stohlman, Stephen A.;Bergmann, Cornelia C.
通讯作者：
Bergmann, Cornelia C.