KLRG1 identifies regulatory T cells with mitochondrial alterations that accumulate with aging
Recent studies using single-cell RNA sequencing technology have uncovered several subpopulations of CD4<sup>+</sup> 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<sup>+</sup> T cell subpopulations. Our analysis identifies a subpopulation of regulatory T (T<sub>reg</sub>) 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 T<sub>reg</sub> cells display senescence features such as mitochondrial alterations, increased expression of cell-cycle regulators and genomic DNA damage. Functionally, KLRG1<sup>+</sup> T<sub>reg</sub> cells show a reduced suppressive activity in vivo accompanied by a pro-inflammatory phenotype.
Authors
- María Beatriz Álvarez Flores (ORCID: https://orcid.org/0000-0002-0292-5010)
- Carlos Torroja (ORCID: https://orcid.org/0000-0001-8914-3400)
- Virginia Zorita (ORCID: https://orcid.org/0009-0003-1527-9737)
- Cristina M. Fernández-Díaz (ORCID: https://orcid.org/0000-0003-0539-7636)
- Fátima Sánchez‐Cabo (ORCID: https://orcid.org/0000-0003-1881-1664)
- David Abia (ORCID: https://orcid.org/0000-0003-0401-7590)
- Elisa Carrasco (ORCID: https://orcid.org/0000-0002-0817-1627)
- Marı́a Mittelbrunn (ORCID: https://orcid.org/0000-0003-3487-8762)
- Manuel M. Gómez de las Heras (ORCID: https://orcid.org/0000-0001-7447-694X)
- Enrique Gabandé‐Rodríguez (ORCID: https://orcid.org/0000-0002-9715-8714)
- Sascha Jung (ORCID: https://orcid.org/0000-0002-3488-409X)
- Isaac Francos-Quijorna (ORCID: https://orcid.org/0000-0003-2514-4206)
- José Ignacio Escrig-Larena (ORCID: https://orcid.org/0000-0002-1538-8808)
- Ana Ramı́rez de Molina (ORCID: https://orcid.org/0000-0003-1439-7494)
- Antonio del Sol (ORCID: https://orcid.org/0000-0002-9926-617X)
- Gonzalo Soto‐Heredero (ORCID: https://orcid.org/0000-0001-8043-7314)
- Eva María Blanco (ORCID: https://orcid.org/0000-0001-5940-1827)
- Sandra Delgado-Pulido (ORCID: https://orcid.org/0000-0003-2055-6594)
- Álvaro Fernández-Almeida (ORCID: https://orcid.org/0009-0006-1483-4585)
- María Josefa Rodríguez
Institutions
- Madrid Institute for Advanced Studies (ES)
- Ikerbasque (ES)
- University of Luxembourg (LU)
- Instituto de Salud Carlos III (ES)
- CIC bioGUNE (ES)
- IMDEA Food (ES)
- Centro de Biología Molecular Severo Ochoa (ES)
- Universidad Autónoma de Madrid (ES)
Publication Details
- Journal
- Nature Aging
- Published
- 2025-04-30
- DOI
- https://doi.org/10.1038/s43587-025-00855-9
- Citations
- 16
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 12.76