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Immunofluorescence Staining Using IBA1 and TMEM119 for Microglial Density, Morphology and Peripheral Myeloid Cell Infiltration Analysis in Mouse Brain
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Immunofluorescence Staining Using IBA1 and TMEM119 for Microglial Density, Morphology and Peripheral Myeloid Cell Infiltration Analysis in Mouse Brain

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T cell-microglial interactions that impair myelin maintenance and regeneration: cellular mechanisms on white-matter

Chaehyun Song1,2, Yoonsung Lee1,2,3, Man S Kim1,2,3

  • 1Translational-Transdisciplinary Research Center, Clinical Research Institute, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Republic of Korea.

Frontiers in Immunology
|June 15, 2026
PubMed

Insights

Aging alters immune cell interactions in the brain, specifically microglia and T cells, leading to white matter damage. This impacts brain aging and neurodegenerative diseases, suggesting new therapeutic targets for myelin repair.

Area of Science:

  • Neuroimmunology
  • Neurodegeneration
  • White Matter Biology

Background:

  • White matter changes, marked by myelin deterioration, are common in aging and neurodegenerative diseases.
  • Microglia and T lymphocytes interact, contributing to white matter pathology.
  • Aging shifts immune cell states, impacting the brain's immune-glial landscape.

Purpose of the Study:

  • To review cellular and molecular evidence on how aging affects microglial and T cell interactions.
  • To explore the mechanisms by which these interactions lead to white matter alterations.
  • To identify therapeutic opportunities for restoring brain homeostasis and promoting remyelination.

Main Methods:

  • Review of cross-species evidence, with a focus on murine models.
  • Analysis of single-cell and spatial transcriptomic data.
  • Integration of molecular, genetic, and cellular insights.

Main Results:

  • Aging alters microglial signaling and promotes CD8+ T cell recruitment via cytokine signaling.
  • T cell-derived interferon-gamma induces transcriptional changes in microglia and oligodendrocyte lineage cells.
  • These interferon-responsive glial states destabilize myelin and impair remyelination.

Conclusions:

  • T cell-microglial interactions are a key mechanism driving white matter alterations in aging.
  • Dysfunctional immune responses in aging brains contribute to neurodegeneration and myelin loss.
  • Targeting these interactions offers therapeutic potential for myelin repair and restoring brain health.
Keywords:
CD8+ T cellsinterferon-gammamicroglianeuroinflammationremyelinationwhite matter aging

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