Ageing impairs the regenerative capacity of regulatory T cells in mouse central nervous system remyelination

Alerie Guzman de la Fuente*, Marie Dittmer, Elise J. Heesbeen, Nira de la Vega Gallardo, Jessica A. White, Andrew Young, Tiree McColgan, Amy Dashwood, Katie Mayne, Sonia Cabeza-Fernández, John Falconer, Francisco Javier Rodriguez-Baena, Christopher E. McMurran, Mohammed Inayatullah, Khalil S. Rawji, Robin J. M. Franklin, James Dooley, Adrian Liston, Rebecca J. Ingram, Vijay K. TiwariRosana Penalva, Yvonne Dombrowski, Denise C. Fitzgerald*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Myelin regeneration (remyelination) is essential to prevent neurodegeneration in demyelinating diseases such as Multiple Sclerosis, however, its efficiency declines with age. Regulatory T cells (Treg) recently emerged as critical players in tissue regeneration, including remyelination. However, the effect of ageing on Treg-mediated regenerative processes is poorly understood. Here, we show that expansion of aged Treg does not rescue age-associated remyelination impairment due to an intrinsically diminished capacity of aged Treg to promote oligodendrocyte differentiation and myelination in male and female mice. This decline in regenerative Treg functions can be rescued by a young environment. We identified Melanoma Cell Adhesion Molecule 1 (MCAM1) and Integrin alpha 2 (ITGA2) as candidates of Treg-mediated oligodendrocyte differentiation that decrease with age. Our findings demonstrate that ageing limits the neuroregenerative capacity of Treg, likely limiting their remyelinating therapeutic potential in aged patients, and describe two mechanisms implicated in Treg-driven remyelination that may be targetable to overcome this limitation.

Original languageEnglish
Article number1870
Number of pages19
JournalNature Communications
Volume15
DOIs
Publication statusPublished - 11 Mar 2024

Keywords

  • Humans
  • Male
  • Female
  • Mice
  • Animals
  • Aged
  • Remyelination/physiology
  • T-Lymphocytes, Regulatory/metabolism
  • Oligodendroglia/physiology
  • Cell Differentiation/physiology
  • Myelin Sheath/metabolism
  • Aging
  • Central Nervous System

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