T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS

被引：277

作者：

Chiu, Isaac M. ^{[1
]}

Chen, Adam ^{[2
]}

Zheng, Yi ^{[1
]}

Kosaras, Bela ^{[3
]}

Tsiftsoglou, Stefanos A. ^{[1
]}

Vartanian, Timothy K. ^{[3
]}

Brown, Robert H., Jr. ^{[2
]}

Carroll, Michael C. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Immune Dis Inst, Dept Pathol, Boston, MA 02115 USA

[2] Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA 02129 USA

[3] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 46期

基金：

美国国家卫生研究院;

关键词：

amyotrophic lateral sclerosis; microglia; neuroimmunology; neuroinflammation; T cells;

D O I：

10.1073/pnas.0804610105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Amyotrophic Lateral Sclerosis (ALS) is an adult-onset, progressive, motor neuron degenerative disease, in which the role of inflammation is not well established. Innate and adaptive immunity were investigated in the CNS of the Superoxide Dismutase 1 (SOD1)(G93A) transgenic mouse model of ALS. CD4(+) and CD8+ T cells infiltrated SOD1(G93A) spinal cords during disease progression. Cell-specific flow cytometry and gene expression profiling showed significant phenotypic changes in microglia, including dendritic cell receptor acquisition, and expression of genes linked to neuroprotection, cholesterol metabolism and tissue remodeling. Microglia dramatically up-regulated IGF-1 and down-regulated IL-6 expression. When mutant SOD1 mice were bred onto a TCR beta deficient background, disease progression was significantly accelerated at the symptomatic stage. In addition, microglia reactivity and IGF-1 levels were reduced in spinal cords of SOD1(G93A) (TCR beta(-/-)) mice. These results indicate that T cells play an endogenous neuroprotective role in ALS by modulating a beneficial inflammatory response to neuronal injury.

引用

页码：17913 / 17918

页数：6

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