ArticleJCI insight2019
Pyruvate kinase M2 is requisite for Th1 and Th17 differentiation.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 98 citations in OpenAlex.
- Metabolic determinants of autoimmune kidney diseases.Nature reviews. Nephrology · 2026Review
- Pyruvate Kinase M2 Upregulation Is Associated With Guillain-Barré Syndrome Risk and Immune Dysregulation: Insights From Mendelian Randomization and the Experimental Autoimmune Neuritis Model.Brain and behavior · 2026Article
- When the Liver Flares: Inflammatory and Immunometabolic Mechanisms Driving the Transition from MASLD to MASH.Inflammation · 2026Review
- Targeting pyruvate kinase M2 (PKM2) reduces T cell pathogenicity in multiple sclerosis.EBioMedicine · 2026Article
- Signal Transducer and Activator of Transcription (STAT) Proteins Regulate Mucosal-Associated Invariant T (MAIT) Cell Function.Immunology · 2026Article
- Pyruvate kinase muscle 2 (PKM2) promotes CD4 T cell survival by regulating pyruvate oxidation during homeostasis and expansion.Science advances · 2026Article
- Roles of immune cell metabolism in rheumatoid arthritis.Frontiers in immunology · 2026Review
- Regulation of CD4 + T cell differentiation and function by glucose metabolism.Genes and immunity · 2025Review
- Targeting lactate metabolism to restore immune homeostasis: a precision therapeutic paradigm for rheumatoid arthritis.Frontiers in immunology · 2025Review
- Metabolic reprogramming as a therapeutic target for modulating the Th17/Treg balance in autoimmune diseases: a comprehensive review.Frontiers in immunology · 2025Review
- Deficiency of metabolic regulator PKM2 activates the pentose phosphate pathway and generates TCF1Nature immunology · 2024Article
- The immunology of systemic lupus erythematosus.Nature immunology · 2024Review
- Tetramerization of pyruvate kinase M2 attenuates graft-versus-host disease by inhibition of Th1 and Th17 differentiation.Human cell · 2024Article
- Article
- T cell metabolism in kidney immune homeostasis.Frontiers in immunology · 2024Review
- Article
- Signaling pathways and targeted therapies for psoriasis.Signal transduction and targeted therapy · 2023Review
- M2 isoform of pyruvate kinase rewires glucose metabolism during radiation therapy to promote an antioxidant response and glioblastoma radioresistance.Neuro-oncology · 2023Article
- Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity.Acta pharmaceutica Sinica. B · 2023Article
- Endosome Traffic Modulates Pro-Inflammatory Signal Transduction in CD4International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
Abstract
Th1 and Th17 are important in the pathogenesis of autoimmune diseases and they depend on glycolysis as a source of energy. T cell antigen receptor signaling phosphorylates a serine/threonine kinase, calcium/calmodulin-dependent protein kinase IV (CaMK4), and promotes glycolysis. Based on these findings we hypothesized that CaMK4 promotes glycolysis. Camk4-deficient CD4+ T cells and cells treated with a CaMK4 inhibitor had less glycolysis compared with their counterparts. Pull-down of CaMK4 and mass spectrometry identified pyruvate kinase muscle isozyme (PKM), the final rate-limiting enzyme in glycolysis, as a binding partner. Coimmunoprecipitation and Western blotting showed that CaMK4 interacts directly with PKM2. Camk4-deficient CD4+ T cells displayed decreased pyruvate kinase activity. Silencing or pharmacological inhibition of PKM2 reduced glycolysis and in vitro differentiation to Th1 and Th17 cells, while PKM2 overexpression restored Th17 cell differentiation. Treatment with a PKM2 inhibitor ameliorated experimental autoimmune encephalomyelitis and CD4+ T cells treated with PKM2 inhibitor or Pkm2-shRNA caused limited disease activity in an adoptive cell transfer model of experimental autoimmune encephalomyelitis. Our data demonstrate that CaMK4 binds to PKM2 and promotes its activity, which is requisite for Th1 and Th17 differentiation in vitro and in vivo. PKM2 represents a therapeutic target for T cell-dependent autoimmune diseases.
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Registered trials
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.