Mitochondrial complex III is essential for suppressive function of regulatory T cells

Samuel E. Weinberg, Benjamin D. Singer, Elizabeth M. Steinert, Carlos A. Martinez, Manan M. Mehta, Inmaculada Martínez-Reyes, Peng Gao, Kathryn A. Helmin, Hiam Abdala-Valencia, Laura A. Sena, Paul T. Schumacker, Laurence A. Turka and Navdeep S. Chandel ()
Additional contact information
Samuel E. Weinberg: Northwestern University Feinberg School of Medicine
Benjamin D. Singer: Northwestern University Feinberg School of Medicine
Elizabeth M. Steinert: Northwestern University Feinberg School of Medicine
Carlos A. Martinez: Northwestern University Feinberg School of Medicine
Manan M. Mehta: Northwestern University Feinberg School of Medicine
Inmaculada Martínez-Reyes: Northwestern University Feinberg School of Medicine
Peng Gao: Northwestern University Feinberg School of Medicine
Kathryn A. Helmin: Northwestern University Feinberg School of Medicine
Hiam Abdala-Valencia: Northwestern University Feinberg School of Medicine
Laura A. Sena: Northwestern University Feinberg School of Medicine
Paul T. Schumacker: Northwestern University Feinberg School of Medicine
Laurence A. Turka: Rheos Medicines
Navdeep S. Chandel: Northwestern University Feinberg School of Medicine

Nature, 2019, vol. 565, issue 7740, 495-499

Abstract: Abstract Regulatory T cells (Treg cells), a distinct subset of CD4+ T cells, are necessary for the maintenance of immune self-tolerance and homeostasis1,2. Recent studies have demonstrated that Treg cells exhibit a unique metabolic profile, characterized by an increase in mitochondrial metabolism relative to other CD4+ effector subsets3,4. Furthermore, the Treg cell lineage-defining transcription factor, Foxp3, has been shown to promote respiration5,6; however, it remains unknown whether the mitochondrial respiratory chain is required for the T cell-suppression capacity, stability and survival of Treg cells. Here we report that Treg cell-specific ablation of mitochondrial respiratory chain complex III in mice results in the development of fatal inflammatory disease early in life, without affecting Treg cell number. Mice that lack mitochondrial complex III specifically in Treg cells displayed a loss of T cell-suppression capacity without altering Treg cell proliferation and survival. Treg cells deficient in complex III showed decreased expression of genes associated with Treg function, whereas Foxp3 expression remained stable. Loss of complex III in Treg cells increased DNA methylation as well as the metabolites 2-hydroxyglutarate (2-HG) and succinate that inhibit the ten-eleven translocation (TET) family of DNA demethylases7. Thus, Treg cells require mitochondrial complex III to maintain immune regulatory gene expression and suppressive function.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (6)

Downloads: (external link)
https://www.nature.com/articles/s41586-018-0846-z Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:565:y:2019:i:7740:d:10.1038_s41586-018-0846-z

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-018-0846-z

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().