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

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

Research output: Contribution to journalArticle

36 Scopus citations

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.

Original languageEnglish (US)
Article numbere06376
JournaleLife
Volume4
Issue numberMAY
DOIs
StatePublished - May 14 2015
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Yang, R., Lirussi, D., Thornton, T. M., Jelley-Gibbs, D. M., Diehl, S. A., Case, L. K., Madesh, M., Taatjes, D. J., Teuscher, C., Haynes, L., & Rincón, M. (2015). Mitochondrial Ca2+ and membrane potential, an alternative pathway for Interleukin 6 to regulate CD4 cell effector function. eLife, 4(MAY), [e06376]. https://doi.org/10.7554/eLife.06376