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

eLife

Douglas J Taatjes¹  Laura Haynes²  Muniswamy Madesh³  Sean A Diehl⁴  Rui Yang⁴  Dario Lirussi⁴  Laure K Case⁴  Tina M Thornton⁴  Mercedes Rincón⁴  Cory Teuscher⁵  Dawn M Jelley-Gibbs⁶ 

[1] Center for Translational Medicine, Temple University, Philadelphia, United States;Microscopy Imaging Center, University of Vermont, Burlington, United States;Department of Medical Genetics and Molecular Biochemistry, Temple University, Philadelphia, United States;Department of Medicine, Immunobiology Program, University of Vermont, Burlington, United States;Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, United States;Trudeau Institute, Saranac Lake, United States;

关键词: mitochondrion;    IL-6;    Stat3;    calcium;    effector cytokine;    NFATc2;   

DOI  :  10.7554/eLife.06376

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown