| Autor: |
Alerie Guzman de la Fuente, Marie Dittmer, Elise Heesbeen, Nira de la Vega Gallardo, Jessica White, Andrew Young, Katie Mayne, John Falconer, Christopher E. McMurran, Mohammed Innayatullah, Rebecca Ingram, Vijay Tiwari, Rosana Penalva, Yvonne Dombrowski, Denise C. Fitzgerald |
| Rok vydání: |
2023 |
| DOI: |
10.1101/2023.01.25.525562 |
| Popis: |
Myelin regeneration (remyelination) is essential to prevent neurodegeneration in demyelinating diseases such as Multiple Sclerosis but 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. 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 novel 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 novel mechanisms implicated in Treg-driven remyelination that may be targetable to overcome this limitation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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