Transcriptomics,Multiomics

Dataset Information

11

HIF1a-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells


ABSTRACT: Upon antigen stimulation, the bioenergetic demands of T cells increase dramatically over the resting state. Although a role for the metabolic switch to glycolysis has been suggested to support increased anabolic activities and facilitate T cell growth and proliferation, whether cellular metabolism controls T cell lineage choices remains poorly understood. Here we report that the glycolytic pathway is actively regulated during the differentiation of inflammatory TH17 and Foxp3-expressing regulatory T cells (Treg), and controls cell fate determination. TH17 but not Treg-inducing conditions resulted in strong upregulation of the glycolytic activity and induction of glycolytic enzymes. Blocking glycolysis inhibited TH17 development while promoting Treg cell generation. Moreover, the transcription factor hypoxia-inducible factor 1a (HIF1a) was selectively expressed in TH17 cells and its induction required signaling through mTOR, a central regulator of cellular metabolism. HIF1a-dependent transcriptional program was important for mediating glycolytic activity, thereby contributing to the lineage choices between TH17 and Treg cells. Lack of HIF1a resulted in diminished TH17 development but enhanced Treg differentiation, and protected mice from autoimmune CNS inflammation. Our studies demonstrate that HIF1a-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. Naïve CD4 T cells from wild-type and HIF1a-deficient mice (in triplicates each group) were differentiated under TH17 conditions for 2.5 days, and RNA was analyzed by microarrays.

OTHER RELATED OMICS DATASETS IN: PRJNA141031

ORGANISM(S): Mus Musculus

SUBMITTER: Lewis Z Shi   Ruoning Wang  Gonghua Huang  Peter Vogel  Hongbo Chi  Geoffrey Neale  David Finkelstein  Douglas R Green 

PROVIDER: E-GEOD-29765 | ArrayExpress | 2011-06-07

SECONDARY ACCESSION(S): GSE29765PRJNA141031

REPOSITORIES: GEO, ArrayExpress

Dataset's files

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E-GEOD-29765.idf.txt Idf
E-GEOD-29765.processed.1.zip Processed
E-GEOD-29765.raw.1.zip Raw
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Publications

HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells.

Shi Lewis Z LZ   Wang Ruoning R   Huang Gonghua G   Vogel Peter P   Neale Geoffrey G   Green Douglas R DR   Chi Hongbo H  

The Journal of experimental medicine 20110627 7


Upon antigen stimulation, the bioenergetic demands of T cells increase dramatically over the resting state. Although a role for the metabolic switch to glycolysis has been suggested to support increased anabolic activities and facilitate T cell growth and proliferation, whether cellular metabolism controls T cell lineage choices remains poorly understood. We report that the glycolytic pathway is actively regulated during the differentiation of inflammatory T(H)17 and Foxp3-expressing regulatory  ...[more]

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