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Mitochondrial Ca2+ and membrane potential, an alternative pathway for Interleukin 6 to regulate CD4 cell effector function

Yang, Rui
; 
Lirussi, Dario
; 
Thornton, Tina M.
; 
Jelley-Gibbs, Dawn M.
; 
Diehl, Sean A.
; 
Case, Laure K.
; ; 
Taatjes, Douglas J.
; 
Teuscher, Cory
; 
Haynes, Laura
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Genre
Journal article
Date
2015-05-14
Advisor
Committee member
Group
Center for Translational Medicine (Temple University)
Department
Medical Genetics and Molecular Biochemistry
Subject
Immunology and Inflammation
 Mitochondrion
 IL-6
 Stat3
 Calcium
 Effector cytokine
 NFATc2
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http://hdl.handle.net/20.500.12613/8740
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Madesh-JournalArticle-2015.pdf
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DOI
https://doi.org/10.7554/elife.06376
Abstract
IL-6 plays an important role in determining the fate of effector CD4 cells and the cytokines that these cells produce. Here we identify a novel molecular mechanism by which IL-6 regulates CD4 cell effector function. We show that IL-6-dependent signal facilitates the formation of mitochondrial respiratory chain supercomplexes to sustain high mitochondrial membrane potential late during activation of CD4 cells. Mitochondrial hyperpolarization caused by IL-6 is uncoupled from the production of ATP by oxidative phosphorylation. However, it is a mechanism to raise the levels of mitochondrial Ca2+ late during activation of CD4 cells. Increased levels of mitochondrial Ca2+ in the presence of IL-6 are used to prolong Il4 and Il21 expression in effector CD4 cells. Thus, the effect of IL-6 on mitochondrial membrane potential and mitochondrial Ca2+ is an alternative pathway by which IL-6 regulates effector function of CD4 cells and it could contribute to the pathogenesis of inflammatory diseases.
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Citation
Rui Yang, Dario Lirussi, Tina M Thornton, Dawn M Jelley-Gibbs, Sean A Diehl, Laure K Case, Muniswamy Madesh, Douglas J Taatjes, Cory Teuscher, Laura Haynes, Mercedes Rincón (2015) Mitochondrial Ca2+ and membrane potential, an alternative pathway for Interleukin 6 to regulate CD4 cell effector function eLife 4:e06376. https://doi.org/10.7554/eLife.06376
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eLife
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eLife, Vol. 4
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