CD4 T cell therapy counteracts inflammaging and senescence by preserving gut barrier integrity

Gómez de las Heras, Manuel M.Carrasco, ElisaPérez Manrique, MarioInohara, NaohiroDelgado Pulido, SandraFernández Almeida, ÁlvaroGálvez Castaño, María I.Francos Quijorna, IsaacSimó, CarolinaGarcía Cañas, VirginiaEscrig Larena, José IgnacioAranda Gómez, Juan FranciscoSoto Heredero, GonzaloGabandé Rodríguez, EnriqueBlanco, Eva MaríaDías Almeida, JoyceNúñez, GabrielMittelbrunn, María2025-09-222025-09-222025-08Gómez 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.adv098510.1126/sciimmunol.adv0985https://hdl.handle.net/20.500.14352/124188Healthy 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.engCD4 T cell therapy counteracts inflammaging and senescence by preserving gut barrier integrityjournal article2470-9468DOI: 10.1126/sciimmunol.adv0985https://www.science.org/doi/10.1126/sciimmunol.adv0985metadata only access577.2612.017InmunologíaBiología molecular (Biología)Biología celular (Biología)2412 Inmunología2302.21 Biología Molecular2407 Biología Celular