STAT3 modulates CD4+ T mitochondrial dynamics and function in aging

被引：4

作者：

Zukowski, Emelia ^{[1
]}

Sannella, Marco ^{[1
]}

Rockhold, Jack Donato ^{[1
]}

Kalantar, Gabriella H. ^{[2
]}

Yu, Jingting ^{[3
]}

SantaCruz-Calvo, Sara ^{[4
,5
]}

Kuhn, Madison K. ^{[6
,7
,8
,9
]}

Hah, Nasun ^{[10
]}

Ouyang, Ling ^{[10
]}

Wang, Tzu-Wen ^{[10
]}

Murphy, Lyanne ^{[11
]}

Marszalkowski, Heather ^{[11
]}

Gibney, Kaleigh ^{[1
]}

Drummond, Micah J. ^{[12
]}

Proctor, Elizabeth A. ^{[6
,7
,8
,9
,13
]}

Hasturk, Hatice ^{[14
]}

Nikolajczyk, Barbara S. ^{[4
,5
]}

Bharath, Leena P. ^{[1
]}

机构：

[1] Merrimack Coll, Dept Nutr & Publ Hlth, N Andover, MA 01845 USA

[2] Univ Kentucky, Dept Microbiol Immunol & Mol Genet, Lexington, KY USA

[3] Salk Inst Biol Studies, Razavi Newman Integrat Genom & Bioinformat Core, La Jolla, CA USA

[4] Univ Kentucky, Dept Pharmacol & Nutr Sci, Lexington, KY USA

[5] Univ Kentucky, Barnstable Brown Diabet & Obes Ctr, Lexington, KY USA

[6] Penn State Univ, Dept Neurosurg, Hershey, PA USA

[7] Penn State Univ, Dept Pharmacol, Hershey, PA USA

[8] Penn State Univ, Dept Biomed Engn, USA7Next, Hershey, PA USA

[9] Penn State Univ, Ctr Neural Engn, Hershey, PA USA

[10] Salk Inst Biol Studies, Next Generat Sequencing Core, La Jolla, CA USA

[11] Merrimack Coll, Dept Biol, N Andover, MA USA

[12] Univ Utah, Dept Phys Therapy & Athlet Training, Salt Lake City, UT USA

[13] Penn State Univ, Dept Engn Sci & Mech, Hershey, PA USA

[14] Forsyth Inst, Cambridge, MA USA

来源：

AGING CELL | 2023年 / 22卷 / 11期

关键词：

aging; CD4(+) T cells; cytokines; inflammaging; mitochondria; mitochondrial STAT3; naive CD4(+) T cells; Th17; ORTHOGONAL PROJECTIONS; CELL-ACTIVATION; PHOSPHO-SER727; MORPHOLOGY; AGE;

D O I：

10.1111/acel.13996

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：15

共 50 条

[1] Prohibitin 1 modulates mitochondrial function of Stat3
Han, Jie
Yu, Chunhua
Souza, Rhonda F.
Theiss, Arianne L.
CELLULAR SIGNALLING, 2014, 26 (10) : 2086 - 2095
[2] Opposing roles of STAT1 and STAT3 in IL-21 function in CD4+ T cells
Wan, Chi-Keung
Andraski, Allison B.
Spolski, Rosanne
Li, Peng
Kazemian, Majid
Oh, Jangsuk
Samsel, Leigh
Swanson, Phillip A., II
McGavern, Dorian B.
Sampaio, Elizabeth P.
Freeman, Alexandra F.
Milner, Joshua D.
Holland, Steven M.
Leonard, Warren J.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (30) : 9394 - 9399
[3] STAT3 in CD4+ T helper cell differentiation and inflammatory diseases
Egwuagu, Charles E.
CYTOKINE, 2009, 47 (03) : 149 - 156
[4] Evaluating the Role of STAT3 in CD4+ T Cells in Susceptibility to Invasive Aspergillosis
Gohir, Wajiha
McTaggart, Lisa
Kus, Julianne, V
Mazzulli, Tony
Kumar, Deepali
Humar, Atul
Husain, Shahid
INFECTION AND IMMUNITY, 2021, 89 (05)
[5] Loss of STAT3 in CD4+ T cells prevents development of experimental autoimmune diseases
Liu, Xuebin
Lee, Yun Sang
Yu, Cheng-Rong
Egwuagu, Charles E.
JOURNAL OF IMMUNOLOGY, 2008, 180 (09): : 6070 - 6076
[6] STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles
Jalila Alshekaili
Rochna Chand
Cindy Eunhee Lee
Susan Corley
Kristy Kwong
Ilenia Papa
David A. Fulcher
Katrina L. Randall
Jennifer W. Leiding
Cindy S. Ma
Marc R. Wilkins
Gulbu Uzel
Chris C. Goodnow
Carola G. Vinuesa
Stuart G. Tangye
Matthew C. Cook
Scientific Reports, 8
[7] Function of Mitochondrial Stat3 in Cellular Respiration
Wegrzyn, Joanna
Potla, Ramesh
Chwae, Yong-Joon
Sepuri, Naresh B. V.
Zhang, Qifang
Koeck, Thomas
Derecka, Marta
Szczepanek, Karol
Szelag, Magdalena
Gornicka, Agnieszka
Moh, Akira
Moghaddas, Shadi
Chen, Qun
Bobbili, Santha
Cichy, Joanna
Dulak, Jozef
Baker, Darren P.
Wolfman, Alan
Stuehr, Dennis
Hassan, Medhat O.
Fu, Xin-Yuan
Avadhani, Narayan
Drake, Jennifer I.
Fawcett, Paul
Lesnefsky, Edward J.
Larner, Andrew C.
SCIENCE, 2009, 323 (5915) : 793 - 797
[8] IL-27 suppresses RANKL expression in CD4+ T cells in part through STAT3
Kamiya, Sadahiro
Okumura, Masae
Chiba, Yukino
Fukawa, Takeshi
Nakamura, Chika
Nimura, Noriyuki
Mizuguchi, Junichiro
Wada, Seiki
Yoshimoto, Takayuki
IMMUNOLOGY LETTERS, 2011, 138 (01) : 47 - 53
[9] The role of STAT3 and AhR in the differentiation of CD4+ T cells into Th17 and Treg cells
Liu, Xingxing
Hu, Hui
Fan, Heng
Zuo, Dongmei
Shou, Zhexing
Liao, Yi
Nan, Zhen
Tang, Qing
MEDICINE, 2017, 96 (17)
[10] Genomic views of STAT function in CD4+ T helper cell differentiation
John J. O'Shea
Riitta Lahesmaa
Golnaz Vahedi
Arian Laurence
Yuka Kanno
Nature Reviews Immunology, 2011, 11 : 239 - 250

← 1 2 3 4 5 →