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Mitochondrial complex III is essential for regulatory T cell suppressive function

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE120452 | GEO | 2018/12/18

REPOSITORIES: GEO

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

Project description: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.

| S-EPMC6345596 | biostudies-literature

Mitochondrial complex III is essential for regulatory T cell suppressive function. [DNA methylation/RRBS]

Project description:Regulatory T cells (Treg cells), a distinct subset of CD4+ T cells, are necessary for the maintenance of immune self-tolerance and homeostasis. Recent studies have demonstrated that Treg cells display a unique metabolic profile characterized by an increase in mitochondrial metabolism relative to other CD4+ effector subsets. Furthermore, the Treg cell lineage-defining transcription factor, Foxp3, has been shown to promote respiration; however, it remains unknown whether the mitochondrial respiratory chain is required for Treg cell suppressive capacity, stability, and survival. Here we report that Treg cell-specific ablation of mitochondrial respiratory chain complex III results in the development of a fatal inflammatory disease early in life, without impacting Treg cell number. Mice lacking complex III specifically in Treg cells displayed a loss of Treg cell suppressive capacity without altering Treg cell proliferation and survival. Treg cells deficient in complex III display decreased expression of genes associated with Treg function while maintaining stable FOXP3 expression. Complex III-null Treg cells displayed increased DNA methylation at the loci of differentially down-regulated genes without a global increase in DNA methylation. Loss of complex III in Treg cells resulted in buildup of the metabolites 2-hydroxyglutarate (2-HG) and succinate that can function as inhibitors of α-ketoglutarate (α−KG)-dependent dioxygenase reactions such as the ten-eleven translocation (TET) family of DNA demethylases. Thus, Treg cells require mitochondrial respiration to maintain immune regulatory gene expression and suppressive function.

2018-12-18 | GSE120451 | GEO

Mitochondrial complex III is essential for regulatory T cell suppressive function. [gene expression/RNA-seq]

2018-12-18 | GSE120449 | GEO

Mitochondrial complex III is essential for regulatory T cell suppressive function

Project description:Mitochondrial complex III is essential for regulatory T cell suppressive function

| PRJNA493083 | ENA

Maintenance DNA methylation is essential for regulatory T cell development and stability of suppressive function

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-08-27 | GSE143974 | GEO

Mitochondrial complex III is essential for regulatory T cell suppressive function. [DNA methylation/RRBS]

Project description:Mitochondrial complex III is essential for regulatory T cell suppressive function. [DNA methylation/RRBS]

| PRJNA493088 | ENA

Mitochondrial regulator CRIF1 deficiency induces Foxp3low inflammatory non-suppressive regulatory-T cells in tumors

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-02-28 | GSE233903 | GEO

Transcriptional repressor HIC1 contributes to suppressive function of human induced regulatory T cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-02-20 | GSE90570 | GEO

SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-11-21 | GSE71506 | GEO

Mitochondrial complex III is essential for regulatory T cell suppressive function. [gene expression/RNA-seq]

Project description:Mitochondrial complex III is essential for regulatory T cell suppressive function. [gene expression/RNA-seq]

| PRJNA493086 | ENA

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