Astrocyte-restricted ablation of interleukin-17-induced Act1-mediated signaling ameliorates autoimmune encephalomyelitis.
Astrocyte-restricted ablation of interleukin-17-induced Act1-mediated signaling ameliorates autoimmune encephalomyelitis.
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DOI：
10.1016/j.immuni.2010.03.004
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发表时间：
2010-03-26
期刊：
影响因子：
32.4
通讯作者：
Li X
中科院分区：
文献类型：
--
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
由辅助性T细胞17（Th 17）分泌的白细胞介素-17（IL-17）在实验性自身免疫性脑脊髓炎（EAE）的发生发展中是必需的。然而，目前尚不清楚IL-17介导的信号传导在不同的细胞区室参与中枢神经系统（CNS）的炎症过程。我们研究了在内皮细胞、巨噬细胞和小胶质细胞以及神经外胚层（神经元、星形胶质细胞和少突胶质细胞）中特异性缺失Act 1（IL-17信号传导所需的关键组分）的小鼠的CNS炎症。在Act 1缺陷小鼠中，Th 17细胞表现出正常的CNS浸润，但未能招募淋巴细胞、中性粒细胞和巨噬细胞。内皮细胞或巨噬细胞和小胶质细胞中的Act 1缺乏对EAE的发展没有实质性影响。然而，神经外胚层来源的CNS驻留细胞中的靶向Act 1缺陷导致EAE的严重程度显著降低。具体而言，Act 1缺陷型星形胶质细胞显示IL-17介导的炎症基因诱导受损。因此，星形胶质细胞在自身免疫诱导的CNS炎症过程中IL-17-Act 1介导的白细胞募集中至关重要。
Interleukin-17 (IL-17) secreted by T helper 17 (Th17) cells is essential in the development of experimental autoimmune encephalomyelitis (EAE). However, it remains unclear how IL-17-mediated signaling in different cellular compartments participates in the central nervous system (CNS) inflammatory process. We examined CNS inflammation in mice with specific deletion of Act1, a critical component required for IL-17 signaling, in endothelial cells, macrophages and microglia, and neuroectoderm (neurons, astrocytes, and oligodendrocytes). In Act1-deficient mice, Th17 cells showed normal infiltration into the CNS but failed to recruit lymphocytes, neutrophils, and macrophages. Act1 deficiency in endothelial cells or in macrophages and microglia did not substantially impact the development of EAE. However, targeted Act1 deficiency in neuroectoderm derived CNS resident cells resulted in markedly reduced severity in EAE. Specifically, Act1-deficient astrocytes showed impaired IL-17-mediated inflammatory gene induction. Thus, astroctyes are critical in IL-17-Act1 mediated leukocyte recruitment during autoimmune induced inflammation of the CNS.
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影响因子：
15.9
作者：
Haak, Stefan;Croxford, Andrew L.;Waisman, Ari
通讯作者：
Waisman, Ari
DOI：
10.1084/jem.20030077
发表时间：
2003-11-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kano A;Wolfgang MJ;Gao Q;Jacoby J;Chai GX;Hansen W;Iwamoto Y;Pober JS;Flavell RA;Fu XY
通讯作者：
Fu XY
影响因子：
3.3
作者：
Halonen, Sandra K.;Woods, Tyson;Weiss, Louis M.
通讯作者：
Weiss, Louis M.
影响因子：
4.4
作者：
Claudio, Estefania;Sonder, Soren Ulrik;Saret, Sun;Carvalho, Gabrielle;Ramalingam, Thirumalai R.;Wynn, Thomas A.;Chariot, Alain;Garcia-Perganeda, Antonio;Leonardi, Antonio;Paun, Andrea;Chen, Amy;Ren, Nina Y.;Wang, Hongshan;Siebenlist, Ulrich
通讯作者：
Siebenlist, Ulrich
T-BET的丧失，但不是STAT1阻止了实验性自身免疫性脑脊髓炎的发展。
影响因子：
15.3
作者：
Bettelli, E;Sullivan, B;Szabo, SJ;Sobel, RA;Glimcher, H;Kuchroo, VK
通讯作者：
Kuchroo, VK