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<p>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.</p>

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KLRG1 identifies regulatory T cells with mitochondrial alterations that accumulate with aging

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月30日

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  • Gonzalo Soto-Heredero,
  • Enrique Gabandé-Rodríguez,
  • Elisa Carrasco,
  • José Ignacio Escrig-Larena,
  • Manuel M. Gómez de las Heras,
  • Sandra Delgado-Pulido,
  • Isaac Francos-Quijorna,
  • Eva M. Blanco,
  • Álvaro Fernández-Almeida,
  • David Abia,
  • María Josefa Rodríguez,
  • Cristina M. Fernández-Díaz,
  • María Beatriz Álvarez-Flores,
  • Ana Ramírez de Molina,
  • Sascha Jung,
  • Antonio del Sol,
  • Virginia Zorita,
  • Fátima Sánchez-Cabo,
  • Carlos Torroja,
  • María Mittelbrunn

摘要

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.