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

ABSTRACT: 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 TCRbeta 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) (TCRbeta-/-) mice. These results indicate that T cells play an endogenous neuroprotective role in ALS by modulating a beneficial inflammatory response to neuronal injury.

SUBMITTER: Chiu IM

PROVIDER: S-EPMC2581614 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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

Chiu Isaac M IM Chen Adam A Zheng Yi Y Kosaras Bela B Tsiftsoglou Stefanos A SA Vartanian Timothy K TK Brown Robert H RH Carroll Michael C MC

Proceedings of the National Academy of Sciences of the United States of America 20081107 46

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 ...[more]

PMID: 18997009

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Dataset Information

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

Publications

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

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