The Role of Th17 Cells in Immunopathogenesis of Neuroinflammatory Disorders

Abstract

Neuroinflammation, characterized by infiltration of immune cells such as T lymphocyte populations and other immune cells, is a prominent pathological feature of neurodegenerative disorders. However, consequence of neural injury during this inflammation is still unclear. Traditionally, CD4+ T helper (Th) cells have been categorized into various subsets. T helper 17 (Th17) cells are a Th subpopulation that plays an important role in the pathogenesis of neuroinflammatory diseases. The chronic forms of inflammatory milieu induce the Th17 cell polarization from their precursors and then secretion of pro-inflammatory cytokines such as interleukin-17 (IL-17), IL-21, IL-22, IL-23, and IL-6. Both interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) from Th17 cells exacerbate the inflammation. Migrating autoreactive Th17 cells into the nervous system can elicit neuronal apoptosis directly via Fas/FasL interaction. Th17 cells increase migration of other immune cells such as neutrophils into the inflamed CNS through the blood-brain barrier (BBB) and trigger the inflammatory reactions that occasionally lead to irreversible neuronal damages. Therefore, it is not surprising that these cells are implicated in a wide range of neuroinflammatory and autoimmune disorders including multiple sclerosis (MS), Alzheimer disease (AD), Parkinson disease (PD), schizophrenia, and many other neuroimmune disorders. In this chapter, we describe the immunopathogenesis of Th17 cells in neuroinflammations and discuss the neuronal injuries induced by Th17 cells and other Th17-related immune cells.