Vollständiger Abstract
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Abstract Age-associated hematopoietic skewing results in an increase in the neutrophil-to-lymphocyte ratio, which serves as a strong predictor of all-cause mortality in older adults, although its causes are incompletely understood. Here we show that cytotoxic CD4 + T lymphocytes accumulate in the bone marrow of mice during aging and induce myelopoiesis, increasing the neutrophil-to-lymphocyte ratio. T cell receptor-dependent induction of mitochondrial stress and activation of STING upregulates the chemokine CCL5 in CD4 + T lymphocytes. During aging, hematopoietic stem cells and downstream myeloid progenitors upregulate CCR5, the primary receptor for CCL5. Genetic ablation of Ccr5 in hematopoietic progenitors mitigates T cell-induced myeloid skewing and neutrophil expansion. Pharmacological blockade of CCR5 using the Food and Drug Administration-approved drug maraviroc normalizes myelopoiesis, reduces circulating and tissue-infiltrating neutrophils, and improves multiple aging-related biomarkers and functional outcomes in aged mice. Together, these findings demonstrate a T cell–bone marrow axis that exacerbates age-associated decline and highlight CCR5 inhibition as a potential geroprotective strategy.
Bibliografischer Nachweis
Publikationsdaten
- Autor:innen
- Enrique Gabandé-Rodríguez, Gonzalo Soto-Heredero, Elisa Carrasco, Carlos Anerillas, José Ignacio Escrig-Larena, Jorge Martínez-Cano, Sandra Delgado-Pulido, Isaac Francos-Quijorna, Gabriela Desdín-Micó, Tatiana Smirnova, Manuel M. Gómez de las Heras, Álvaro Fernández-Almeida, Alice Leandri, Andrea Cugurra, Eva María Blanco, Elia Winand-Osete, Pablo Ramírez-Ruiz de Erenchun, Virginia Zorita, Camilla Bean, Valentin Basset, Françoise Solly, Amanda Garrido, Rafael de Cabo, Santos Mañes, Manolis Pasparakis, Matteo Iannacone, César Cobaleda, Olaia Naveiras, Myriam Gorospe, María Mittelbrunn
- Quelle
- Nature Aging
- Publikation
- 2026-01-01
- Band / Ausgabe
- Nicht angegeben
- Seiten
- Nicht angegeben
- ISSN / ISBN
- 2662-8465
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Zitierfähiger Nachweis
Enrique Gabandé-Rodríguez, Gonzalo Soto-Heredero, Elisa Carrasco, Carlos Anerillas, José Ignacio Escrig-Larena, Jorge Martínez-Cano, Sandra Delgado-Pulido, Isaac Francos-Quijorna, Gabriela Desdín-Micó, Tatiana Smirnova, Manuel M. Gómez de las Heras, Álvaro Fernández-Almeida, Alice Leandri, Andrea Cugurra, Eva María Blanco, Elia Winand-Osete, Pablo Ramírez-Ruiz de Erenchun, Virginia Zorita, Camilla Bean, Valentin Basset, Françoise Solly, Amanda Garrido, Rafael de Cabo, Santos Mañes, Manolis Pasparakis, Matteo Iannacone, César Cobaleda, Olaia Naveiras, Myriam Gorospe, María Mittelbrunn (2026). Cytotoxic CD4+ T cells induce age-associated myelopoiesis through CCL5–CCR5 signaling. Nature Aging. https://doi.org/10.1038/s43587-026-01209-9
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