T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS Academic Article uri icon

Overview

MeSH Major

  • Amyotrophic Lateral Sclerosis
  • Cytoprotection
  • Inflammation
  • Neurons
  • T-Lymphocytes

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.

publication date

  • November 18, 2008

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2581614

Digital Object Identifier (DOI)

  • 10.1073/pnas.0804610105

PubMed ID

  • 18997009

Additional Document Info

start page

  • 17913

end page

  • 8

volume

  • 105

number

  • 46