ArticleThe Journal of clinical investigation2024
Lactate supports Treg function and immune balance via MGAT1 effects on N-glycosylation in the mitochondria.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed.
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- Autoimmune disease patients with comorbid cancer exhibit prominent immunometabolic crosstalk.Science China. Life sciences · 2026Article
- Glycosylation modification: a trigger for obesity and its complications?Molecular medicine (Cambridge, Mass.) · 2026Review
- Article
- Targeting the cancer metabolism-immunity interface: update and perspectives.Experimental hematology & oncology · 2026Review
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- Lactate metabolism and epigenetic reprogramming drive c-KIT hyperactivation to mediate Gilteritinib resistance: Rationale for c-KIT degraders over kinase inhibitors.Acta pharmaceutica Sinica. B · 2026Article
- Immune cross talk and therapeutic advances in lactate metabolism in the tumor microenvironment (Review).Experimental and therapeutic medicine · 2026Review
- Glucose metabolic reprogramming as a driver of immunosuppression in the tumour microenvironment.Clinical and translational medicine · 2026Review
- The Metabolic Calibration of Female Immune Plasticity: From X-Linked Vulnerability to Precision Metabotyping.Biology · 2026Review
- Review
- Targeting metabolic reprogramming to enhance adoptive immunotherapy: emerging mechanisms and translational perspectives.Journal of translational medicine · 2026Review
- The role of lactate on arthritis-associated cells: physiology, pathology, and therapeutic strategies.Cellular and molecular life sciences : CMLS · 2026Review
- Tumor microenvironment dynamics in gastric cancer pathogenesis and therapeutic resistance.Molecular cancer · 2026Review
- Targeting mitochondrial homeostasis as a cancer treatment strategy: current status and future prospects.Molecular cancer · 2026Review
- Lipid Metabolism in Regulatory T Cells in Health and Disease.Journal of inflammation research · 2026Review
- Immunosuppressive cells as barriers to cancer therapy: mechanisms and emerging solutions.Frontiers in immunology · 2026Review
- Immune remodeling of tumor-draining lymph nodes: mechanistic determinants of checkpoint blockade responsiveness.Frontiers in immunology · 2026Review
- The double-edged sword of regulatory T cells in MASLD: from inflammation control to fibrosis promotion.Animal cells and systems · 2026Review
- Regulatory T cells in autoimmune diseases: biological mechanisms, clinical translation, and translational challenges.Frontiers in immunology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors.
Funding
Abstract
Current research reports that lactate affects Treg metabolism, although the precise mechanism has only been partially elucidated. In this study, we presented evidence demonstrating that elevated lactate levels enhanced cell proliferation, suppressive capabilities, and oxidative phosphorylation (OXPHOS) in human Tregs. The expression levels of Monocarboxylate Transporters 1/2/4 (MCT1/2/4) regulate intracellular lactate concentration, thereby influencing the varying responses observed in naive Tregs and memory Tregs. Through mitochondrial isolation, sequencing, and analysis of human Tregs, we determined that α-1,3-Mannosyl-Glycoprotein 2-β-N-Acetylglucosaminyltransferase (MGAT1) served as the pivotal driver initiating downstream N-glycosylation events involving progranulin (GRN) and hypoxia-upregulated 1 (HYOU1), consequently enhancing Treg OXPHOS. The mechanism by which MGAT1 was upregulated in mitochondria depended on elevated intracellular lactate that promoted the activation of XBP1s. This, in turn, supported MGAT1 transcription as well as the interaction of lactate with the translocase of the mitochondrial outer membrane 70 (TOM70) import receptor, facilitating MGAT1 translocation into mitochondria. Pretreatment of Tregs with lactate reduced mortality in a xenogeneic graft-versus-host disease (GvHD) model. Together, these findings underscored the active regulatory role of lactate in human Treg metabolism through the upregulation of MGAT1 transcription and its facilitated translocation into the mitochondria.
Indexed as
Identifiers
What OpenQuestion holds
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.