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M.M. is supported by the Miguel Servet Program (CP 19/014, Fundacion de Investigacion del Hospital 12 de Octubre; the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (PI19/855), the European Regional Development Fund (ERDF), and the European Commission through H2020-EU.1.1 and European Research Council grant ERC-2016-StG 715322-EndoMitTalk. G.K. is supported by the Ligue contre le Cancer (equipe labellisee); Agence National de la Recherche (ANR) - Projets blancs; AMMICa US23/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Association 'Ruban Rose'; Canceropole Ile-de-France; Chancelerie des universites de Paris (Legs Poix), Fondation pour la Recherche Medicale (FRM); a donation by Elior; European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR); Gustave Roussy Odyssea, the European Union Horizon 2020 Project Oncobiome; Fondation Carrefour; High-end Foreign Expert Program in China (GDW20171100085), Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; LeDucq Foundation; the LabEx Immuno-Oncology (ANR-18-IDEX-0001); the RHU Torino Lumiere; the Seerave Foundation; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and the SIRIC Cancer Research and Personalized Medicine (CARPEM). This study contributes to the IdEx Universite de Paris ANR-18-IDEX-0001.

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Hallmarks of T cell aging

Publicado en:NATURE IMMUNOLOGY. 22 (6): 687-698 - 2021-05-13 22(6), DOI: 10.1038/s41590-021-00927-z

Autores: Mittelbrunn, Maria; Kroemer, Guido

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Resumen

In this Review, Mittelbrunn and Kroemer propose that ten molecular hallmarks represent the common denominators of T cell aging. The aged adaptive immune system is characterized by progressive dysfunction as well as increased autoimmunity. This decline is responsible for elevated susceptibility to infection and cancer, as well as decreased vaccination efficacy. Recent evidence indicates that CD4(+) T cell-intrinsic alteratins contribute to chronic inflammation and are sufficient to accelerate an organism-wide aging phenotype, supporting the idea that T cell aging plays a major role in body-wide deterioration. In this Review, we propose ten molecular hallmarks to represent common denominators of T cell aging. These hallmarks are grouped into four primary hallmarks (thymic involution, mitochondrial dysfunction, genetic and epigenetic alterations, and loss of proteostasis) and four secondary hallmarks (reduction of the TCR repertoire, naive-memory imbalance, T cell senescence, and lack of effector plasticity), and together they explain the manifestation of the two integrative hallmarks (immunodeficiency and inflammaging). A major challenge now is weighing the relative impact of these hallmarks on T cell aging and understanding their interconnections, with the final goal of defining molecular targets for interventions in the aging process.

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