Article (Scientific journals)
KLRG1 identifies regulatory T cells with mitochondrial alterations that accumulate with aging.
Soto-Heredero, Gonzalo; Gabandé-Rodríguez, Enrique; Carrasco, Elisa et al.
2025In Nature Aging
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Abstract :
[en] Recent studies using single-cell RNA sequencing technology have uncovered several subpopulations of CD4+ T cells that accumulate with aging. These age-associated T cells are emerging as relevant players in the onset of inflammaging and tissue senescence. Here, based on information provided by single-cell RNA sequencing data, we present a flow cytometry panel that allows the identification of age-associated T cell subsets in systematic larger analysis in mice. We use this panel to evaluate at the single-cell level mitochondrial and senescence marks in the different age-associated CD4+ T cell subpopulations. Our analysis identifies a subpopulation of regulatory T (Treg) cells that is characterized by the extracellular expression of the co-inhibitory molecule killer cell lectin-like receptor subfamily G member 1 (KLRG1) and accumulates with aging in humans and mice. KLRG1-expressing Treg cells display senescence features such as mitochondrial alterations, increased expression of cell-cycle regulators and genomic DNA damage. Functionally, KLRG1+ Treg cells show a reduced suppressive activity in vivo accompanied by a pro-inflammatory phenotype.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Soto-Heredero, Gonzalo ;  Departamento de Biología Molecular, Facultad de Ciencias, Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid, Madrid, Spain ; Consejo Superior de Investigaciones Científicas, Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid, Madrid, Spain
Gabandé-Rodríguez, Enrique ;  Departamento de Biología Molecular, Facultad de Ciencias, Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid, Madrid, Spain ; Consejo Superior de Investigaciones Científicas, Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid, Madrid, Spain
Carrasco, Elisa ;  Departamento de Biología, Facultad de Ciencias, Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid, Madrid, Spain
Escrig-Larena, José Ignacio ;  Consejo Superior de Investigaciones Científicas, Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid, Madrid, Spain
Gómez de Las Heras, Manuel M ;  Departamento de Biología Molecular, Facultad de Ciencias, Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid, Madrid, Spain
Delgado-Pulido, Sandra ;  Consejo Superior de Investigaciones Científicas, Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid, Madrid, Spain
Francos-Quijorna, Isaac;  Departamento de Biología Molecular, Facultad de Ciencias, Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid, Madrid, Spain ; Consejo Superior de Investigaciones Científicas, Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid, Madrid, Spain
Blanco, Eva M ;  Consejo Superior de Investigaciones Científicas, Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid, Madrid, Spain
Fernández-Almeida, Álvaro ;  Consejo Superior de Investigaciones Científicas, Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid, Madrid, Spain
Abia, David ;  Consejo Superior de Investigaciones Científicas, Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid, Madrid, Spain
Rodríguez, María Josefa;  Servicio de Microscopía Electrónica, Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid, Madrid, Spain
Fernández-Díaz, Cristina M;  IMDEA Food Institute, CEI UAM+CSIC, Madrid, Spain
Álvarez-Flores, María Beatriz ;  Centro Nacional de Investigaciones Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain
Ramírez de Molina, Ana;  IMDEA Food Institute, CEI UAM+CSIC, Madrid, Spain
Jung, Sascha;  Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch sur-Alzette, Luxembourg ; CIC bioGUNE-BRTA (Basque Research and Technology Alliance), Bizkaia Technology Park, Derio, Spain ; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
DEL SOL MESA, Antonio  ;  University of Luxembourg ; CIC bioGUNE-BRTA (Basque Research and Technology Alliance), Bizkaia Technology Park, Derio, Spain ; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
Zorita, Virginia;  Centro Nacional de Investigaciones Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain
Sánchez-Cabo, Fátima;  Centro Nacional de Investigaciones Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain
Torroja, Carlos ;  Centro Nacional de Investigaciones Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain
Mittelbrunn, María ;  Consejo Superior de Investigaciones Científicas, Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid, Madrid, Spain. mmittelbrunn@cbm.csic.es
More authors (10 more) Less
External co-authors :
yes
Language :
English
Title :
KLRG1 identifies regulatory T cells with mitochondrial alterations that accumulate with aging.
Publication date :
30 April 2025
Journal title :
Nature Aging
eISSN :
2662-8465
Publisher :
Springer Science and Business Media LLC, United States
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 02 May 2025

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