ArticleNature communications2014
HGK/MAP4K4 deficiency induces TRAF2 stabilization and Th17 differentiation leading to insulin resistance.
Article in Nature communications, 2014. 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, 88 citations in OpenAlex.
- MAP4K2 suppresses antitumor immunity in a pancreatic cancer model by promoting Treg differentiation.The Journal of clinical investigation · 2026Article
- Obesity and type 2 diabetes as chronic inflammation: how does the cytokine evidence align?Frontiers in endocrinology · 2026Review
- The role of dietary inflammatory index in metabolic diseases: the associations, mechanisms, and treatments.European journal of clinical nutrition · 2025Review
- Machine learning-based prediction reveals kinase MAP4K4 regulates neutrophil differentiation through phosphorylating apoptosis-related proteins.PLoS computational biology · 2025Article
- The novel anthraquinone compound Kanglexin prevents endothelial-to-mesenchymal transition in atherosclerosis by activating FGFR1 and suppressing integrin β1/TGFβ signaling.Frontiers of medicine · 2024Article
- Association of Serum Adipsin Level with Insulin Resistance and Inflammatory Markers in Newly Diagnosed Type two Diabetes Mellitus Patients.Indian journal of clinical biochemistry : IJCB · 2024Article
- Cathelicidin Antimicrobial Peptide Levels in Atherosclerosis and Myocardial Infarction in Mice and Human.International journal of molecular sciences · 2024Article
- Exploration of the core pathway of inflammatory bowel disease complicated with metabolic fatty liver and two-sample Mendelian randomization study of the causal relationships behind the disease.Frontiers in immunology · 2024Article
- The natural compound Sanggenon C inhibits PRRSV infection by regulating the TRAF2/NF-κB signalling pathway.Veterinary research · 2023Article
- Weight loss improves inflammation by T helper 17 cells in an obese patient with psoriasis at high risk for cardiovascular events.Journal of diabetes investigation · 2023Article
- Co-Expression Analysis of Airway Epithelial Transcriptome in Asthma Patients with Eosinophilic vs. Non-Eosinophilic Airway Infiltration.International journal of molecular sciences · 2023Article
- Adipose tissue aging is regulated by an altered immune system.Frontiers in immunology · 2023Review
- Metabolic influences on T cell in psoriasis: a literature review.Frontiers in immunology · 2023Review
- MAP4K4 and cancer: ready for the main stage?Frontiers in oncology · 2023Review
- Bioinformatics and Experimental Analyses Reveal MAP4K4 as a Potential Marker for Gastric Cancer.Genes · 2022Article
- Review
- The Role of Tumor Necrosis Factor Associated Factors (TRAFs) in Vascular Inflammation and Atherosclerosis.Frontiers in cardiovascular medicine · 2022Review
- The role of Th17 cells in endocrine organs: Involvement of the gut, adipose tissue, liver and bone.Frontiers in immunology · 2022Review
- The molecular basis of the dichotomous functionality of MAP4K4 in proliferation and cell motility control in cancer.Frontiers in oncology · 2022Review
- MAP4K4 mediates the SOX6-induced autophagy and reduces the chemosensitivity of cervical cancer.Cell death & disease · 2021Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
Proinflammatory cytokines play important roles in insulin resistance. Here we report that mice with a T-cell-specific conditional knockout of HGK (T-HGK cKO) develop systemic inflammation and insulin resistance. This condition is ameliorated by either IL-6 or IL-17 neutralization. HGK directly phosphorylates TRAF2, leading to its lysosomal degradation and subsequent inhibition of IL-6 production. IL-6-overproducing HGK-deficient T cells accumulate in adipose tissue and further differentiate into IL-6/IL-17 double-positive cells. Moreover, CCL20 neutralization or CCR6 deficiency reduces the Th17 population or insulin resistance in T-HGK cKO mice. In addition, leptin receptor deficiency in T cells inhibits Th17 differentiation and improves the insulin sensitivity in T-HGK cKO mice, which suggests that leptin cooperates with IL-6 to promote Th17 differentiation. Thus, HGK deficiency induces TRAF2/IL-6 upregulation, leading to IL-6/leptin-induced Th17 differentiation in adipose tissue and subsequent insulin resistance. These findings provide insight into the reciprocal regulation between the immune system and the metabolism.
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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.