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. Tiwari, Rosana Penalva, Yvonne Dombrowski and Denise C. Fitzgerald ()
Additional contact information
Alerie Guzman de la Fuente: Queen’s University Belfast
Marie Dittmer: Queen’s University Belfast
Elise J. Heesbeen: Queen’s University Belfast
Nira de la Vega Gallardo: Queen’s University Belfast
Jessica A. White: Queen’s University Belfast
Andrew Young: Queen’s University Belfast
Tiree McColgan: Queen’s University Belfast
Amy Dashwood: University of Cambridge
Katie Mayne: Queen’s University Belfast
Sonia Cabeza-Fernández: Institute for Health and Biomedical Sciences of Alicante (ISABIAL)
John Falconer: Queen’s University Belfast
Francisco Javier Rodriguez-Baena: Instituto de Neurosciencias CSIC-UMH, San Juan de Alicante
Christopher E. McMurran: University of Cambridge
Mohammed Inayatullah: University of Southern Denmark
Khalil S. Rawji: Altos Labs - Cambridge Institute of Science, Granta Park
Robin J. M. Franklin: Altos Labs - Cambridge Institute of Science, Granta Park
James Dooley: University of Cambridge
Adrian Liston: University of Cambridge
Rebecca J. Ingram: Queen’s University Belfast
Vijay K. Tiwari: Queen’s University Belfast
Rosana Penalva: Queen’s University Belfast
Yvonne Dombrowski: Queen’s University Belfast
Denise C. Fitzgerald: Queen’s University Belfast

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-45742-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45742-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-45742-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().