ArticleProceedings of the National Academy of Sciences of the United States of America2011
The D-dopachrome tautomerase (DDT) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF).
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers, 1 of them a synthesis that pooled it.
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Who cites it
140 citing papers in PubMed, 1 synthesis or guideline pooled it, 223 citations in OpenAlex.
- Macrophage migration inhibitory factor as a diagnostic and predictive biomarker in sepsis: meta-analysis of clinical trials.Scientific reports · 2021Pooled it
- Cell-type-specific damage scores reveal kidney and liver disease trajectories in single-cell and spatial transcriptomics.Cell genomics · 2026Article
- Circulating MIF, D-DT, and Soluble CD74 in End-Stage Heart Failure Patients Receiving LVAD: An Exploratory Clinical Study and Effects on Adult Cardiac Myofibroblasts.Biomedicines · 2026Article
- Single-cell eQTL mapping reveals cell-type-specific genetic regulation in lung cancer.Cell genomics · 2026Article
- Pathogenic role of MIF receptor (CD74) expressing T cells in inflammatory arthritis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Using 4-HPP and PP as Substrates to Assess Purified MIF and D-DT Tautomerase Activity and Inhibition.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Generation of High-Quality D-Dopachrome Tautomerase Crystals for Structural Studies.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Stable Transfection of CD74 Gene Variants into A549 Lung Adenocarcinoma Cell Line.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Expression and Purification of Recombinant D-Dopachrome Tautomerase (D-DT).Methods in molecular biology (Clifton, N.J.) · 2026Article
- Detection of Noncovalent Protein-Ligand Complexes of D-DT Variants by MALDI-TOF Mass Spectrometry.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Review
- Targeting macrophage migration inhibitory factor as a potential therapeutic strategy in colorectal cancer.Oncogenesis · 2025Article
- The multifaced role of the macrophage migration inhibitory factor family in organ fibrosis.American journal of physiology. Cell physiology · 2025Review
- Inhibition of MIF with an Allosteric Inhibitor Triggers Cell Cycle Arrest in Acute Myeloid Leukemia.ACS omega · 2025Article
- MIF as an oncogenic driver of low-heterogeneity melanomas.Molecular oncology · 2025Article
- An atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis.Nature communications · 2025Article
- Single-cell mRNA analysis and surface marker expression profiling of circulating immune cells in humans with alpha-gal syndrome.Frontiers in immunology · 2025Article
- The distinct functions of MIF in inflammatory cardiomyopathy.Frontiers in immunology · 2025Review
- Usp18 Mediates D-Dopachrome Tautomerase-Induced Astrocytic Inflammation After Spinal Cord Injury.Journal of inflammation research · 2025Article
- Leveraging dynamic stability to infer regulation in protein-protein interaction networks: A study of infectious vulnerability in COPD.PloS one · 2025Article
80 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Macrophage migration inhibitory factor (MIF) is a pivotal regulator of the immune response. Neutralization or genetic deletion of MIF does not completely abrogate activation responses, however, and deletion of the MIF receptor, CD74, produces a more pronounced phenotype than MIF deficiency. We hypothesized that these observations may be explained by a second MIF-like ligand, and we considered a probable candidate to be the protein encoded by the homologous, D-dopachrome tautomerase (D-DT) gene. We show that recombinant D-DT protein binds CD74 with high affinity, leading to activation of ERK1/2 MAP kinase and downstream proinflammatory pathways. Circulating D-DT levels correlate with disease severity in sepsis or malignancy, and the specific immunoneutralization of D-DT protects mice from lethal endotoxemia by reducing the expression of downstream effector cytokines. These data indicate that D-DT is a MIF-like cytokine with an overlapping spectrum of activities that are important for our understanding of MIF-dependent physiology and pathology.
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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.