TY - JOUR
T1 - STAT3 modulates CD4+ T mitochondrial dynamics and function in aging
AU - Zukowski, Emelia
AU - Sannella, Marco
AU - Rockhold, Jack Donato
AU - Kalantar, Gabriella H.
AU - Yu, Jingting
AU - SantaCruz-Calvo, Sara
AU - Kuhn, Madison K.
AU - Hah, Nasun
AU - Ouyang, Ling
AU - Wang, Tzu Wen
AU - Murphy, Lyanne
AU - Marszalkowski, Heather
AU - Gibney, Kaleigh
AU - Drummond, Micah J.
AU - Proctor, Elizabeth A.
AU - Hasturk, Hatice
AU - Nikolajczyk, Barbara S.
AU - Bharath, Leena P.
N1 - Publisher Copyright:
© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
PY - 2023/11
Y1 - 2023/11
N2 - Aging 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.
AB - Aging 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.
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U2 - 10.1111/acel.13996
DO - 10.1111/acel.13996
M3 - Article
C2 - 37837188
AN - SCOPUS:85174143476
SN - 1474-9718
VL - 22
JO - Aging cell
JF - Aging cell
IS - 11
M1 - e13996
ER -