Related Experiment Video

Updated: Oct 23, 2025

An Ex vivo Model of an Oligodendrocyte-directed T-Cell Attack in Acute Brain Slices
06:36

An Ex vivo Model of an Oligodendrocyte-directed T-Cell Attack in Acute Brain Slices

Published on: February 5, 2015

7.2K

Pro-inflammatory T helper 17 directly harms oligodendrocytes in neuroinflammation

Catherine Larochelle1,2, Beatrice Wasser3, Hélène Jamann2

  • 1Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; zipp@uni-mainz.de catherine.larochelle.chum@ssss.gouv.qc.ca.

Proceedings of the National Academy of Sciences of the United States of America
|August 21, 2021
PubMed

Insights

T helper 17 (Th17) cells directly damage myelin in multiple sclerosis (MS) by forming stable contacts with oligodendrocytes. Blocking CD29, an integrin on Th17 cells, protects against this Th17-mediated injury.

Area of Science:

  • Neuroimmunology
  • Cellular Biology
  • Pathology

Background:

  • T helper 17 (Th17) cells are implicated in inflammatory diseases like multiple sclerosis (MS).
  • Their precise role in central nervous system (CNS) inflammation in MS remains debated.
  • Oligodendrocytes, crucial for myelin production, are targets in MS pathogenesis.

Purpose of the Study:

  • To investigate the direct interaction between Th17 cells and oligodendrocytes in MS.
  • To elucidate the mechanisms by which Th17 cells impact myelin and oligodendrocytes.
  • To identify potential therapeutic targets for mitigating Th17-mediated damage in MS.

Main Methods:

  • In vivo and ex vivo imaging of CNS inflammatory processes in MS models and human MS brains.
  • Co-culture experiments with human and murine Th17 cells and oligodendrocytes.
  • Single-cell RNA-sequencing to analyze cellular responses and molecular pathways.
  • Functional assays assessing demyelination, oligodendrocyte damage, and cell death.
  • Pharmacological blockade of CD29 and glutamate pathways.

Main Results:

  • CNS-infiltrating Th17 cells form stable, prolonged contacts with oligodendrocytes.
  • Direct Th17 cell contact exacerbates experimental demyelination and damages human oligodendrocyte processes, increasing cell death compared to Th2 cells.
  • Human and murine Th17 cells express higher levels of CD29, a molecule linked to glutamate release.
  • Th17 cell interaction with oligodendrocytes triggers glutamate release, inducing oligodendrocyte stress and altering lipid/cholesterol biosynthesis.
  • Glutamate exposure impairs myelination, while CD29 blockade protects oligodendrocytes from Th17-induced injury.

Conclusions:

  • Th17 cells directly attack the myelin compartment in MS through a CD29-dependent mechanism involving glutamate release.
  • This interaction leads to oligodendrocyte damage, cell stress, and impaired myelination.
  • Targeting the CD29 pathway presents a potential therapeutic strategy for MS by preventing Th17-mediated oligodendrocyte injury.
Keywords:
CD29 blockadeTh17 cellsglutamateintravital microscopyoligodendrocytes

More Related Videos

Generation of Oligodendrocytes and Oligodendrocyte-Conditioned Medium for Co-Culture Experiments09:05

Generation of Oligodendrocytes and Oligodendrocyte-Conditioned Medium for Co-Culture Experiments

Published on: February 9, 2020

10.8K
Improved 3D Hydrogel Cultures of Primary Glial Cells for In Vitro Modelling of Neuroinflammation09:19

Improved 3D Hydrogel Cultures of Primary Glial Cells for In Vitro Modelling of Neuroinflammation

Published on: December 8, 2017

15.1K

Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.6K
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
13.1K
Neurogenesis and Regeneration of Nervous Tissue01:15

Neurogenesis and Regeneration of Nervous Tissue

In the CNS, neurogenesis, the birth of new neurons from stem cells, is limited to the hippocampus in adults. In other regions of the brain and spinal cord, neurogenesis is almost non-existent due to inhibitory influences from neuroglia, especially oligodendrocytes, and the absence of growth-stimulating cues. The myelin produced by oligodendrocytes in the CNS inhibits neuronal regeneration. Furthermore, astrocytes proliferate rapidly after neuronal damage, forming scar tissue that physically...
1.2K