The Role of Regulatory T Cells and Microglia in Amyotrophic Lateral Sclerosis

David Beers, Weihua Zhao, Kristopher G. Hooten, Stanley H. Appel

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Neuroinflammation is now established as an important factor in the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), a devastating disorder that causes a selective, rapidly progressing, and irreversible loss of motoneurons. ALS is a noncell autonomous disorder, in which neurons do not die alone, but numerous other cell types play critical roles in disease initiation and progression. The pathogenic processes underlying ALS are multifactorial, and different mechanisms of motoneuron injury and death have been proposed, including a dysregulated neuroinflammatory response. The now well-accepted concept is that the immune system, both innate and adaptive, plays early and important neuroinflammatory roles in disease pathophysiology. At early phases of disease, the immune system contributes to neuroprotective functions, whereas later in disease, the immune system contributes to motoneuron injury. At various time points, microglia and T cells are markedly activated, producing either neuroprotective or proinflammatory molecules, which can decrease or increase the rate of primary motoneuron degeneration, respectively. Recent research has shown that this neuroinflammatory component is affected by the peripheral immune system; T lymphocytes in particular are able to cross into the brain and spinal cord parenchyma, where they interact with resident microglia, inducing them to adopt either an M1 (cytotoxic) or an M2 (protective) phenotype, depending on the stage of disease. This chapter reviews the proposed mechanisms of neuroinflammation in the context of motoneuron interactions with microglia and T cells, specifically regulatory T cells, and the protective or injurious responses provided by these cells, on the basis of what occurs in patients with ALS and animal models of ALS.

Original languageEnglish (US)
Title of host publicationNeuroinflammation
Subtitle of host publicationNew Insights into Beneficial and Detrimental Functions
EditorsS. David
PublisherWiley
Pages235-249
Number of pages15
ISBN (Electronic)9781118732748
ISBN (Print)9781118732823
DOIs
StatePublished - Mar 6 2015

Keywords

  • Amyotrophic lateral sclerosis
  • Macrophage polarization
  • Microglia
  • Neurodegeneration
  • Neuroinflammation
  • T regulatory cells

ASJC Scopus subject areas

  • Medicine(all)
  • Neuroscience(all)

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