Publication in detail

Nature. 2019 Jan;565(7740):495-499. doi: 10.1038/s41586-018-0846-z. Epub 2019 Jan 9.

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

Weinberg, SE; Singer, BD; Steinert, EM; Martinez, CA; Mehta, MM; Martinez-Reyes, I; Gao, P; Helmin, KA; Abdala-Valencia, H; Sena, LA; Schumacker, PT; Turka, LA; Chandel, NS

Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Robert H. Lurie Cancer Center Metabolomics Core, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Rheos Medicines, Cambridge, MA, USA.

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.

ยป Online Version

Proven Track Record

The team at Ozgene has over two decades of experience creating customised knockout and knock-in mice for pivotal medical research globally. Over 400 scientific publications are based on research using Ozgene mice.

Go to Publications

Global Client Base

Ozgene generates genetically customised mice for researchers around the world. Ozgene mice can be found in 31 different countries on 5 continents from small academic institutions to multinational pharmaceutical companies.

See Client Papers

Lean Management

Ozgene is applying Lean Management principles to deliver the highest quality services and shortest lead times to our customers. The implementation of Lean Culture has already seen an improvement in our processes and timelines.

Read More