2023-06-222023-06-222015-05-14Rui 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.063762050-084Xhttp://dx.doi.org/10.34944/dspace/8704http://hdl.handle.net/20.500.12613/8740IL-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.22 pagesengPublic Domainhttp://creativecommons.org/publicdomain/zero/1.0/Immunology and InflammationMitochondrionIL-6Stat3CalciumEffector cytokineNFATc2Text