Evidence map›Paper›PMID 27573366›Full record

ArticleCytokine2016

Modeling of both shared and distinct interactions between MIF and its homologue D-DT with their common receptor CD74.

Roberto Meza-Romero, Gil Benedek, Kelley Jordan, Lin Leng, Georgios Pantouris, Elias Lolis, Richard Bucala, Arthur A Vandenbark

Open access · greenAbstract read
In one paragraph

Article in Cytokine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 25 citations in OpenAlex.

  1. MIF Tautomerase Inhibition Protects Neurons From Immune-Mediated Cell Death.Neurology(R) neuroimmunology & neuroinflammation · 2026
    Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. MIF contribution to progressive brain diseases.Journal of neuroinflammation · 2024
    Review
  9. The role of CD74 in cardiovascular disease.Frontiers in cardiovascular medicine · 2022
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. MIF and D-DT are potential disease severity modifiers in male MS subjects.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  15. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Roberto Meza-RomeroNeuroimmunology Research, VA Portland Health Care System, 3710 SW US Veterans Hosp. Rd, Portland, OR, USA; Tykeson MS Research Laboratory, Department of Neurology UHS-46, 3181 SW Sam Jackson Park Rd, Oregon Health & Science University, Portland, OR, USA.
Gil BenedekNeuroimmunology Research, VA Portland Health Care System, 3710 SW US Veterans Hosp. Rd, Portland, OR, USA; Tykeson MS Research Laboratory, Department of Neurology UHS-46, 3181 SW Sam Jackson Park Rd, Oregon Health & Science University, Portland, OR, USA.
Kelley JordanNeuroimmunology Research, VA Portland Health Care System, 3710 SW US Veterans Hosp. Rd, Portland, OR, USA; Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA.
Lin LengDepartment of Internal Medicine, Yale University School of Medicine, 330 Cedar St, New Haven, CT 06520, USA.
Georgios PantourisDepartment of Pharmacology, Yale School of Medicine, 333 Cedar St, New Haven, CT 06510, USA.
Elias LolisDepartment of Pharmacology, Yale School of Medicine, 333 Cedar St, New Haven, CT 06510, USA; Yale Cancer Center, Yale School of Medicine, 333 Cedar St, New Haven, CT 06510, USA.
Richard BucalaDepartment of Internal Medicine, Yale University School of Medicine, 330 Cedar St, New Haven, CT 06520, USA; Yale Cancer Center, Yale School of Medicine, 333 Cedar St, New Haven, CT 06510, USA.
Arthur A VandenbarkNeuroimmunology Research, VA Portland Health Care System, 3710 SW US Veterans Hosp. Rd, Portland, OR, USA; Tykeson MS Research Laboratory, Department of Neurology UHS-46, 3181 SW Sam Jackson Park Rd, Oregon Health & Science University, Portland, OR, USA; Department of Molecular Microbiology & Immunology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, USA. Electronic address: vandenba@ohsu.edu.
VA Portland Health Care System · USYale University · USYale Cancer Center · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Mechanisms of Rheumatoid Synovial Fibroblast ActivationR01AR049610 · NIAMS · YALE UNIVERSITY · PI BUCALA, RICHARD J · 2002 to 2018
$5.0M
MIF AND THE HOST RESPONSE TO INFECTIONR01AI042310 · NIAID · YALE UNIVERSITY · PI BUCALA, RICHARD J · 1998 to 2013
$4.3M
Development of DRα1-MOG-35-55 for treatment of DR2 negative MS subjectsR44AI122574 · NIAID · VIROGENOMICS BIODEVELOPMENT, INC. · PI SHIRLEY, RENEE LYNN, VANDENBARK, ARTHUR A. · 2020 to 2022
$3.0M
Development of DRα1-MOG-35-55 for treatment of DR2 negative MS subjectsR42AI122574 · NIAID · VIROGENOMICS BIODEVELOPMENT, INC. · PI VANDENBARK, ARTHUR A. · 2017 to 2018
$1.5M
MIF and Host Response to InfectionR56AI042310 · NIAID · YALE UNIVERSITY · PI BUCALA, RICHARD J · 2014 to 2014
$426k
Development of DRα1-MOG-35-55 for treatment of DR2 negative MS subjectsR41AI122574 · NIAID · VIROGENOMICS BIODEVELOPMENT, INC. · PI VANDENBARK, ARTHUR A. · 2016 to 2016
$225k
Immunoregulation of Myelin-Specific T LymphocytesI01BX000226 · VA · PORTLAND VA MEDICAL CENTER · PI VANDENBARK, ARTHUR A. · 2009 to 2024
–
BLRD VA I01 BX000226NCATS NIH HHS UL1 TR001863NIAID NIH HHS R01 AI042310NIAID NIH HHS R41 AI122574NIAID NIH HHS R42 AI122574NIAID NIH HHS R44 AI122574NIAID NIH HHS R56 AI042310NIAMS NIH HHS R01 AR049610
6 · The paper itself

Abstract

D-dopachrome tautomerase (D-DT) shares amino acid sequence similarity, structural architecture and biological activity with the cytokine MIF. Recent studies show that the two protein homologs also bind to the same cell surface receptor, CD74, to activate the ERK1/2 pathway that ultimately leads to pro-inflammatory and pro-survival gene expression. We recently showed that RTL1000 and DRa1-MOG-35-55, two biological drugs with potent anti-inflammatory properties that treat experimental autoimmune encephalomyelitis (EAE) in mice, bind to the cell surface receptor CD74 with high affinity and compete with MIF for binding to the same regions of CD74. Computational modeling of MIF and RTL1000 binding interactions with CD74 predicted the presence of three CD74 binding regions for each MIF homotrimer. Through a similar approach we have now expanded our work to study the D-DT (MIF-2) interaction with CD74 that is mainly defined by three elements scattered throughout the disordered regions of the interacting molecules. The model predicted: (a) a hydrophobic cradle between CD74 and D-DT consisting of N-terminal tyrosine residues of three CD74 monomers arranged in a planar alignment interacts with aromatic amino acid residues located in the disordered D-DT C-terminus; (b) a triad consisting of the E103 residue on one D-DT monomer in close contact with R179 and S181 on one chain of the CD74 trimer forms an intermolecular salt bridge; and (c) amino acid residues on the C-terminus random coil of CD74 chain C form a long interacting area of ∼500Å

Indexed as

Molecular Docking SimulationAntigens, Differentiation, B-LymphocyteHistocompatibility Antigens Class IIHumansIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsProtein DomainsProtein Structure, QuaternaryAntigens, Differentiation, B-Lymphocytedopachrome isomeraseHistocompatibility Antigens Class IIIntramolecular Oxidoreductasesinvariant chainMacrophage Migration-Inhibitory FactorsMIF protein, humanCD74D-DTInflammatory factorsMIFPredicted binding interactions

Identifiers

PMID27573366
PMCPMC5067215
OpenAlexW2514093547

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.