ArticleProceedings of the National Academy of Sciences of the United States of America2016
MIF allele-dependent regulation of the MIF coreceptor CD44 and role in rheumatoid arthritis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
52 citing papers in PubMed, 2 syntheses or guidelines pooled it, 88 citations in OpenAlex.
- Association ofFrontiers in endocrinology · 2025Pooled it
- Pooled it
- Gene expression and immune cell heterogeneity in inbred Amur tiger.BMC genomics · 2026Article
- Single-Cell Mapping Reveals MIF-Centered Immunoregulatory Networks in Colorectal Cancer.International journal of molecular sciences · 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
- A Novel Prognostic Signature Composed of Autophagy and Liver Metastasis in Colorectal Cancer: Comprehensive Analysis of Bulk and Single-Cell Transcriptomic Data.ImmunoTargets and therapy · 2026Article
- Review
- TScience immunology · 2025Article
- Galectin-9 inhibition of the MIF-CD74/CD44 pathway suppresses chronic arthritis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- A 2D inflammatory co-culture model for investigating synovial fibroblast and macrophage interactions in rheumatoid arthritis.Scientific reports · 2025Article
- Increased macrophage migration inhibitory factor is associated with inflammation in patients with rheumatoid arthritis.Clinical rheumatology · 2025Article
- An atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis.Nature communications · 2025Article
- Role of a new truncated CD74 isoform in increased IL-17 secretion from stromal-immune cell interactions.Clinical and experimental immunology · 2025Article
- Regulation of reactive oxygen species and the role of mitochondrial apoptotic-related genes in rheumatoid arthritis.Scientific reports · 2025Article
- Targeting the CD74 signaling axis suppresses inflammation and rescues defective hematopoiesis inScience translational medicine · 2025Article
- The distinct functions of MIF in inflammatory cardiomyopathy.Frontiers in immunology · 2025Review
- Personalized neoantigen hydrogel vaccine combined with PD-1 and CTLA-4 double blockade elicits antitumor response in liver metastases by activating intratumoral CD8Journal for immunotherapy of cancer · 2024Article
- WISP1 and Macrophage Migration Inhibitory Factor in Respiratory Inflammation: Novel Insights and Therapeutic Potentials for Asthma and COPD.International journal of molecular sciences · 2024Review
- Get Spliced: Uniting Alternative Splicing and Arthritis.International journal of molecular sciences · 2024Review
- Targeting low levels of MIF expression as a potential therapeutic strategy for ALS.Cell reports. Medicine · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 5 institutions in 4 countries.
Funding
Abstract
Fibroblast-like synoviocytes mediate joint destruction in rheumatoid arthritis and exhibit sustained proinflammatory and invasive properties. CD44 is a polymorphic transmembrane protein with defined roles in matrix interaction and tumor invasion that is also a signaling coreceptor for macrophage migration inhibitory factor (MIF), which engages cell surface CD74. High-expression MIF alleles (rs5844572) are associated with rheumatoid joint erosion, but whether MIF signaling through the CD74/CD44 receptor complex promotes upstream autoimmune responses or contributes directly to synovial joint destruction is unknown. We report here the functional regulation of CD44 by an autocrine pathway in synovial fibroblasts that is driven by high-expression MIF alleles to up-regulate an inflammatory and invasive phenotype. MIF increases CD44 expression, promotes its recruitment into a functional signal transduction complex, and stimulates alternative exon splicing, leading to expression of the CD44v3-v6 isoforms associated with oncogenic invasion. CD44 recruitment into the MIF receptor complex, downstream MAPK and RhoA signaling, and invasive phenotype require MIF and CD74 and are reduced by MIF pathway antagonists. These data support a functional role for high-MIF expression alleles and the two-component CD74/CD44 MIF receptor in rheumatoid arthritis and suggest that pharmacologic inhibition of this pathway may offer a specific means to interfere with progressive joint destruction.
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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.