KLRG1 identifies regulatory T cells with mitochondrial alterations that accumulate with aging
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 María Blanco, Álvaro Fernández-Almeida, David Abia, María Josefa Rodríguez, Cristina M. Fernández-Díaz, María Beatriz Álvarez Flores, Ana Ramı́rez de Molina, Sascha Jung, Antonio del Sol, Virginia Zorita, Fátima Sánchez‐Cabo, Carlos Torroja, Marı́a Mittelbrunn
Abstract
Abstract 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 (T reg ) 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 reg cells display senescence features such as mitochondrial alterations, increased expression of cell-cycle regulators and genomic DNA damage. Functionally, KLRG1 + T reg cells show a reduced suppressive activity in vivo accompanied by a pro-inflammatory phenotype.