RT Journal Article
T1 CD4 T cell therapy counteracts inflammaging and senescence by preserving gut barrier integrity
A1 Gómez de las Heras, Manuel M.
A1 Carrasco, Elisa
A1 Pérez Manrique, Mario
A1 Inohara, Naohiro
A1 Delgado Pulido, Sandra
A1 Fernández Almeida, Álvaro
A1 Gálvez Castaño, María I.
A1 Francos Quijorna, Isaac
A1 Simó, Carolina
A1 García Cañas, Virginia
A1 Escrig Larena, José Ignacio
A1 Aranda Gómez, Juan Francisco
A1 Soto Heredero, Gonzalo
A1 Gabandé Rodríguez, Enrique
A1 Blanco, Eva María
A1 Días Almeida, Joyce
A1 Núñez, Gabriel
A1 Mittelbrunn, María
AB Healthy aging relies on a symbiotic host-microbiota relationship. The age-associated decline of the immune system can pose a threat to this delicate equilibrium. In this work, we investigated how the functional deterioration of T cells can affect host-microbiota symbiosis and gut barrier integrity and the implications of this deterioration for inflammaging, senescence, and health decline. Using the Tfamfl/flCd4Cre mouse model, we found that T cell failure compromised gut immunity leading to a decrease in T follicular cells and regulatory T cells (Treg cells) and an accumulation of highly proinflammatory and cytotoxic T cells. These alterations were associated with intestinal barrier disruption and gut dysbiosis. Microbiota depletion or adoptive transfer of total CD4 T cells or a Treg cell–enriched pool prevented gut barrier dysfunction and mitigated premature inflammaging and senescence, ultimately enhancing the health span in this mouse model. Thus, a competent CD4 T cell compartment is critical to ensure healthier aging by promoting host-microbiota mutualism and gut barrier integrity.
PB American Association for the Advancement of Science
YR 2025
FD 2025-08
LK https://hdl.handle.net/20.500.14352/124188
UL https://hdl.handle.net/20.500.14352/124188
LA eng
NO Gómez de Las Heras, M. M., Carrasco, E., Pérez-Manrique, M., Inohara, N., Delgado-Pulido, S., Fernández-Almeida, Á., Gálvez-Castaño, M. I., Francos-Quijorna, I., Simó, C., García-Cañas, V., Escrig-Larena, J. I., Aranda, J. F., Soto-Heredero, G., Gabandé-Rodríguez, E., Blanco, E. M., Días-Almeida, J., Núñez, G., & Mittelbrunn, M. (2025). CD4 T cell therapy counteracts inflammaging and senescence by preserving gut barrier integrity. Science immunology, 10(110), eadv0985. https://doi.org/10.1126/sciimmunol.adv0985
DS Docta Complutense
RD 20 mar 2026