Th17 cell, the new player of neuroinflammatory process in multiple sclerosis

Scand J Immunol. 2011 Jul;74(1):1-13. doi: 10.1111/j.1365-3083.2011.02536.x.


Multiple sclerosis (MS) is an autoimmune disease characterized by recurrent episodes of demyelination and axonal lesion mediated by CD4(+) T cells with a proinflammatory Th1 and Th17 phenotype, macrophages, and soluble inflammatory mediators. Identification of Th17 cells led to breaking the dichotomy of Th1/Th2 axis in immunopathogenesis of autoimmune diseases such as MS, and its experimental model, experimental autoimmune encephalomyelitis (EAE). Th17 cells are characterized by expression of retinoic acid-related orphan receptor (ROR)γt and signal transducer and activator of transcription 3 (STAT3) factors. Th17-produced cytokine profile including interleukin (IL)-17, IL-6, IL-21, IL-22, IL-23 and tumour necrosis factor (TNF)-α, which have proinflammatory functions, suggests it as an important factor in immunopathogenesis of MS, because the main feature of MS pathophysiology is the neuroinflammatory reaction. The blood brain barrier (BBB) disruption is an early and central event in MS pathogenesis. Autoreactive Th17 cells can migrate through the BBB by the production of cytokines such as IL-17 and IL-22, which disrupt tight junction proteins in the central nervous system (CNS) endothelial cells. Consistent with this observation and regarding the wide range production of proinflammatory cytokines and chemokines by Th17 cells, it is expected that Th17 cell to be as a potent pathogenic factor in disease immunopathophysiology. Th17-mediated inflammation is characterized by neutrophil recruitment into the CNS and neurons killing. However, the majority of our knowledge about the role of Th17 in MS pathogenesis is resulted in investigation into EAE animal models. In this review, we intend to focus on the newest information regarding the precise role of Th17 cells in immunopathogenesis of MS, and its animal model, EAE.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Movement
  • Central Nervous System / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Humans
  • Inflammation / immunology*
  • Mice
  • Multiple Sclerosis / immunology*
  • Th17 Cells / immunology*