ArticleThe Journal of clinical investigation2015
Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 464 papers.
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Who cites it
464 citing papers in PubMed, 704 citations in OpenAlex.
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- Modulating Th17/Treg Balance in Alzheimer's Disease: Therapeutic Insights from Natural Compounds and Immunometabolism.Brain sciences · 2026Review
- ODC1 restricts meningeal B cell age-associated-like phenotype and function in multiple sclerosis: A human and experimental study.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Sepsis and the immunometabolic inflammatory response.npj metabolic health and disease · 2026Review
- Pyruvate kinase muscle 2 (PKM2) promotes CD4 T cell survival by regulating pyruvate oxidation during homeostasis and expansion.Science advances · 2026Article
- The role and significance of the PI3K/Akt-mTOR signaling pathway in infectious diseases.Frontiers in cellular and infection microbiology · 2026Review
- Divergent immunometabolic reprogramming in psoriasis and atopic dermatitis: a tale of two inflammatory skin diseases.Frontiers in immunology · 2026Review
- Natural polysaccharides as immunometabolic modulators in metabolic diseases: mechanisms and translational challenges.Frontiers in immunology · 2026Review
- Metabolic cell competition in the glioblastoma tumour microenvironment: glucose, glutamine, and lactate as determinants of immune exclusion and targets for pharmacological reprogramming.Frontiers in oncology · 2026Review
- Age-related reduction of pyruvate dehydrogenase kinase 1 impairs T cell responses.Frontiers in immunology · 2026Article
- From high-salt diet to cancer immunity: gut microbiota and immune system interactions and their mechanisms.Frontiers in immunology · 2026Review
- Mitochondrial transfer: a novel paradigm for wound healing.Burns & trauma · 2026Review
- Fueling bone loss: the immunometabolic reprogramming of the bone microenvironment in diabetic osteoporosis.Frontiers in immunology · 2026Review
- Tumor microenvironment-induced epigenetic reprogramming of Tregs and its impact on immunotherapy.Frontiers in genetics · 2026Review
404 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 2 countries.
Funding
Abstract
Activation of CD4+ T cells results in rapid proliferation and differentiation into effector and regulatory subsets. CD4+ effector T cell (Teff) (Th1 and Th17) and Treg subsets are metabolically distinct, yet the specific metabolic differences that modify T cell populations are uncertain. Here, we evaluated CD4+ T cell populations in murine models and determined that inflammatory Teffs maintain high expression of glycolytic genes and rely on high glycolytic rates, while Tregs are oxidative and require mitochondrial electron transport to proliferate, differentiate, and survive. Metabolic profiling revealed that pyruvate dehydrogenase (PDH) is a key bifurcation point between T cell glycolytic and oxidative metabolism. PDH function is inhibited by PDH kinases (PDHKs). PDHK1 was expressed in Th17 cells, but not Th1 cells, and at low levels in Tregs, and inhibition or knockdown of PDHK1 selectively suppressed Th17 cells and increased Tregs. This alteration in the CD4+ T cell populations was mediated in part through ROS, as N-acetyl cysteine (NAC) treatment restored Th17 cell generation. Moreover, inhibition of PDHK1 modulated immunity and protected animals against experimental autoimmune encephalomyelitis, decreasing Th17 cells and increasing Tregs. Together, these data show that CD4+ subsets utilize and require distinct metabolic programs that can be targeted to control specific T cell populations in autoimmune and inflammatory diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.