ArticleThe Journal of clinical investigation2019
Enhanced glycolytic metabolism supports transmigration of brain-infiltrating macrophages in multiple sclerosis.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 136 citations in OpenAlex.
- Monocyte abundance and glycolytic reprogramming associate with motivational impairment in depression.Brain, behavior, and immunity · 2026Article
- Dynamic metabolic programming of monocyte-derived cells defines immunity in CNS disease.Brain : a journal of neurology · 2026Review
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- Intestinal and Blood-Brain Barrier Dysfunction in Lupus: Emerging Mechanisms and Modulation by Cinnamon.Molecules (Basel, Switzerland) · 2026Review
- Plasma GDF15 affects long-term dementia risk and alters neuroimmune signaling.Science advances · 2026Article
- Monocarboxylate transporter 2 regulates maintenance of myelin and axonal integrity by oligodendrocytes.Nature communications · 2026Article
- Oncogenic PIK3CA mutations shape an immunoregulatory microenvironment in mosaic overgrowth disorders.PNAS nexus · 2026Article
- Identification of Immune-Related Lactylation Genes in Rheumatoid Arthritis With Atherosclerosis: A Comprehensive Analysis Using Bulk and Single-Cell RNA Sequencing Data.Mediators of inflammation · 2026Article
- Mediterranean Pattern Diet in Multiple Sclerosis: A Review Focusing on Immunometabolites.Current neuropharmacology · 2026Review
- Early prediction of severe autoimmune encephalitis: development and validation of a model incorporating readily available lactate dehydrogenase.Frontiers in immunology · 2026Article
- Macrophage metabolic reprogramming in organ transplantation: mechanisms, transplant outcomes, and therapeutic implications.Frontiers in cellular and infection microbiology · 2026Review
- Metabolic Programming Drives Protective and Inflammatory Monocyte Fates in Viral Encephalitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- RVG engineered extracellular vesicles-transmitted miR-137 improves autism by modulating glucose metabolism and neuroinflammation.Molecular psychiatry · 2025Article
- Article
- Review
- FABP7 is increased in progressive multiple sclerosis and induces a pro-inflammatory phenotype in monocytes through a glycolytic switch.Nature communications · 2025Article
- Article
- High Fat Low Carbohydrate Diet Is Linked to CNS Autoimmunity Protection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ubiquitination-mediated upregulation of glycolytic enzyme MCT4 in promoting astrocyte reactivity during neuroinflammation.Journal of neuroinflammation · 2025Article
- Catalpalactone protects rats nerve function from hypoxic lesion by polarizing microglial cells toward M2 phenotype.European journal of medical research · 2025Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The migration of leukocytes into the CNS drives the neuropathology of multiple sclerosis (MS). This penetration likely utilizes energy resources that remain to be defined. Using the experimental autoimmune encephalomyelitis (EAE) model of MS, we determined that macrophages within the perivascular cuff of post-capillary venules are highly glycolytic as manifested by strong expression of lactate dehydrogenase A (LDHA) that converts pyruvate to lactate. These macrophages expressed prominent levels of monocarboxylate transporter-4 (MCT-4) specialized in secreting lactate from glycolytic cells. The functional relevance of glycolysis was confirmed by siRNA-mediated knockdown of LDHA and MCT-4, which decreased lactate secretion and macrophage transmigration. MCT-4 was in turn regulated by EMMPRIN (CD147) as determined through co-expression/co-immunoprecipitation studies, and siRNA-mediated EMMPRIN silencing. The functional relevance of MCT-4/EMMPRIN interaction was affirmed by lower macrophage transmigration in culture using the MCT-4 inhibitor, α-cyano-4-hydroxy-cinnamic acid (CHCA), a cinnamon derivative. CHCA also reduced leukocyte infiltration and the clinical severity of EAE. Relevance to MS was corroborated by the strong expression of MCT-4, EMMPRIN and LDHA in perivascular macrophages in MS brains. These results detail the metabolism of macrophages for transmigration from perivascular cuffs into the CNS parenchyma and identifies CHCA and diet as potential modulators of neuro-inflammation in MS.
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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.