TY - JOUR
T1 - Ageing impairs the regenerative capacity of regulatory T cells in mouse central nervous system remyelination
AU - de la Fuente, Alerie Guzman
AU - Dittmer, Marie
AU - Heesbeen, Elise J.
AU - de la Vega Gallardo, Nira
AU - White, Jessica A.
AU - Young, Andrew
AU - McColgan, Tiree
AU - Dashwood, Amy
AU - Mayne, Katie
AU - Cabeza-Fernández, Sonia
AU - Falconer, John
AU - Rodriguez-Baena, Francisco Javier
AU - McMurran, Christopher E.
AU - Inayatullah, Mohammed
AU - Rawji, Khalil S.
AU - Franklin, Robin J.M.
AU - Dooley, James
AU - Liston, Adrian
AU - Ingram, Rebecca J.
AU - Tiwari, Vijay K.
AU - Penalva, Rosana
AU - Dombrowski, Yvonne
AU - Fitzgerald, Denise C.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-024-45742-w
DO - 10.1038/s41467-024-45742-w
M3 - Journal article
C2 - 38467607
AN - SCOPUS:85187481135
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1870
ER -