Dataset Information

Extracellular Delivery of Functional Mitochondria Rescues the Dysfunction of CD4⁺ T Cells in Aging.

ABSTRACT: Mitochondrial dysfunction alters cellular metabolism, increases tissue oxidative stress, and may be principal to the dysregulated signaling and function of CD4⁺ T lymphocytes in the elderly. In this proof of principle study, it is investigated whether the transfer of functional mitochondria into CD4⁺ T cells that are isolated from old mice (aged CD4⁺ T cells), can abrogate aging-associated mitochondrial dysfunction, and improve the aged CD4⁺ T cell functionality. The results show that the delivery of exogenous mitochondria to aged non-activated CD4⁺ T cells led to significant mitochondrial proteome alterations highlighted by improved aerobic metabolism and decreased cellular mitoROS. Additionally, mito-transferred aged CD4⁺ T cells showed improvements in activation-induced TCR-signaling kinetics displaying markers of activation (CD25), increased IL-2 production, enhanced proliferation ex vivo. Importantly, immune deficient mouse models (RAG-KO) showed that adoptive transfer of mito-transferred naive aged CD4⁺ T cells, protected recipient mice from influenza A and Mycobacterium tuberculosis infections. These findings support mitochondria as targets of therapeutic intervention in aging.

SUBMITTER: Headley CA

PROVIDER: S-EPMC10837346 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Extracellular Delivery of Functional Mitochondria Rescues the Dysfunction of CD4+ T Cells in Aging.

Headley Colwyn A CA Gautam Shalini S Olmo-Fontanez Angelica A Garcia-Vilanova Andreu A Dwivedi Varun V Akhter Anwari A Schami Alyssa A Chiem Kevin K Ault Russell R Zhang Hao H Cai Hong H Whigham Alison A Delgado Jennifer J Hicks Amberlee A Tsao Philip S PS Gelfond Jonathan J Martinez-Sobrido Luis L Wang Yufeng Y Torrelles Jordi B JB Turner Joanne J

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20231121 5

Mitochondrial dysfunction alters cellular metabolism, increases tissue oxidative stress, and may be principal to the dysregulated signaling and function of CD4+ T lymphocytes in the elderly. In this proof of principle study, it is investigated whether the transfer of functional mitochondria into CD4+ T cells that are isolated from old mice (aged CD4+ T cells), can abrogate aging-associated mitochondrial dysfunction, and improve the aged CD4+ T cell fun ...[more]

PMID: 37990641

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Dataset Information

Extracellular Delivery of Functional Mitochondria Rescues the Dysfunction of CD4⁺ T Cells in Aging.

Publications

Extracellular Delivery of Functional Mitochondria Rescues the Dysfunction of CD4<sup>+</sup> T Cells in Aging.

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