Regulatory T Cells Contribute to Reduced Myelination in the Aging Brain

Myelin surrounds the axons that connect neurons to one another, and is required for the transmission of electrical impulses. This myelin sheath is maintained by oligodendrocytes. These cells do not carry out their work in isolation; a great many factors are involved in determining the size and capabilities of the oligodendrocyte population. Aging is disruptive to the myelination carried out by oligodendrocytes. The consequences are not as bad as the profound loss of myelin that takes place in demyelinating diseases such as multiple sclerosis, but age-related loss of myelination does appear to degrade cognitive function. Researchers are thus interested in understanding the mechanisms involved, in search of ways to restore a youthful capacity for myelination in the aging brain.

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.


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