<scp>STAT3</scp>modulates<scp>CD4</scp><sup>+</sup>T mitochondrial dynamics and function in aging-Reference-Cited by-同舟云学术

STAT3modulatesCD4⁺T mitochondrial dynamics and function in aging

Published:2023-10-13 Issue:11 Volume:22 Page:
ISSN:1474-9718
Container-title:Aging Cell
language:en
Short-container-title:Aging Cell

Author:

Zukowski Emelia¹,Sannella Marco¹,Rockhold Jack Donato¹,Kalantar Gabriella H.²,Yu Jingting³,SantaCruz‐Calvo Sara⁴⁵,Kuhn Madison K.⁶,Hah Nasun⁷,Ouyang Ling⁷,Wang Tzu‐Wen⁷,Murphy Lyanne⁸,Marszalkowski Heather⁸,Gibney Kaleigh¹,Drummond Micah J.⁹,Proctor Elizabeth A.⁶¹⁰,Hasturk Hatice¹¹,Nikolajczyk Barbara S.⁴⁵^ORCID,Bharath Leena P.¹^ORCID

Affiliation:

1. Department of Nutrition and Public Health Merrimack College North Andover Massachusetts USA

2. Department of Microbiology, Immunology and Molecular Genetics University of Kentucky Lexington Kentucky USA

3. Razavi Newman Integrative Genomics and Bioinformatics Core The Salk Institute for Biological Studies La Jolla California USA

4. Departments of Pharmacology and Nutritional Sciences University of Kentucky Lexington Kentucky USA

5. Barnstable Brown Diabetes and Obesity Center University of Kentucky Lexington Kentucky USA

6. Departments of Neurosurgery, Pharmacology, and Biomedical Engineering and Center for Neural Engineering Pennsylvania State University Hershey Pennsylvania USA

7. Next Generation Sequencing Core The Salk Institute for Biological Studies La Jolla California USA

8. Department of Biology Merrimack College North Andover Massachusetts USA

9. Department of Physical Therapy and Athletic Training University of Utah Salt Lake City Utah USA

10. Department of Engineering Science & Mechanics Pennsylvania State University Hershey Pennsylvania USA

11. Forsyth Institute Cambridge Massachusetts USA

Abstract

AbstractAging promotes numerous intracellular changes in T cells that impact their effector function. Our data show that aging promotes an increase in the localization of STAT3 to the mitochondria (mitoSTAT3), which promotes changes in mitochondrial dynamics and function and T‐cell cytokine production. Mechanistically, mitoSTAT3 increased the activity of aging T‐cell mitochondria by increasing complex II. Limiting mitoSTAT3 using a mitochondria‐targeted STAT3 inhibitor, Mtcur‐1 lowered complex II activity, prevented age‐induced changes in mitochondrial dynamics and function, and reduced Th17 inflammation. Exogenous expression of a constitutively phosphorylated form of STAT3 in T cells from young adults mimicked changes in mitochondrial dynamics and function in T cells from older adults and partially recapitulated aging‐related cytokine profiles. Our data show the mechanistic link among mitoSTAT3, mitochondrial dynamics, function, and T‐cell cytokine production.

Funder

National Institutes of Health

Publisher

Wiley

Subject

Cell Biology,Aging

Link

https://onlinelibrary.wiley.com/doi/pdf/10.1111/acel.13996

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