Evidence map›Paper›PMID 33372156›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

UFMylation inhibits the proinflammatory capacity of interferon-γ-activated macrophages.

Dale R Balce, Ya-Ting Wang, Michael R McAllaster, Bria F Dunlap, Anthony Orvedahl, Barry L Hykes, Lindsay Droit, Scott A Handley, Craig B Wilen, John G Doench and 3 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 2 pooled it
2.0field-weighted citation impact, top 12% 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

35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Article
  6. The mechanistic basis and cellular functions of UFMylation.Nature reviews. Molecular cell biology · 2026
    Review
  7. UFMylation of Pyruvate Dehydrogenase Regulates Mitochondrial Metabolism.bioRxiv : the preprint server for biology · 2026
    Article
  8. Review
  9. Review
  10. Article
  11. Progress on multifunctional transmembrane protein ATG9A.Cell communication and signaling : CCS · 2025
    Review
  12. Review
  13. Review
  14. Proximity biotinylation at the host-bioRxiv : the preprint server for biology · 2025
    Article
  15. Review
  16. Article
  17. Review
  18. UFMylation Modulates OFIP Stability and Centrosomal Localization.Journal of clinical laboratory analysis · 2025
    Article
  19. Article
  20. Article
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

13 authors at 4 institutions in 1 country.

Dale R BalceDepartment of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110; dbalce@vir.bio svirgin@vir.bio.
Ya-Ting WangDepartment of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Michael R McAllasterDepartment of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Bria F DunlapDepartment of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Anthony OrvedahlDepartment of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.ORCID 0000-0002-2481-9200
Barry L HykesDepartment of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Lindsay DroitDepartment of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Scott A HandleyDepartment of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.ORCID 0000-0002-2143-6570
Craig B WilenDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06510.ORCID 0000-0003-2495-9403
John G DoenchBroad Institute of MIT and Harvard, Cambridge, MA 02142.ORCID 0000-0002-3707-9889
Robert C OrchardDepartment of Immunology and Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Christina L StallingsDepartment of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.ORCID 0000-0002-2747-5618
Herbert W VirginDepartment of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110; dbalce@vir.bio svirgin@vir.bio.ORCID 0000-0001-8580-7628
Washington University in St. Louis · USBroad Institute · USThe University of Texas Southwestern Medical Center · USYale University · US

Funding

RP5: Chemical proteomic discovery of small-molecule probes for autophagy proteinsU19AI142784 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI SHILOH, MICHAEL · 2019 to 2023
$36.9M
Genetic and Pathway Analysis CoreU19AI109725 · NIAID · WASHINGTON UNIVERSITY · PI VIRGIN, HERBERT W · 2014 to 2018
$32.7M
Autophagy proteins in the immune response to Mycobacterium tuberculosis infectionR01AI132697 · NIAID · WASHINGTON UNIVERSITY · PI STALLINGS, CHRISTINA LEIGH · 2019 to 2023
$2.4M
Identification and Characterization of Norovirus Cofactors for EntryR00DK116666 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI ORCHARD, ROBERT C. · 2018 to 2020
$747k
NIAID NIH HHS R01 AI132697NIAID NIH HHS U19 AI109725NIAID NIH HHS U19 AI142784NIDDK NIH HHS R00 DK116666
6 · The paper itself

Abstract

Macrophages activated with interferon-γ (IFN-γ) in combination with other proinflammatory stimuli, such as lipopolysaccharide or tumor necrosis factor-α (TNF-α), respond with transcriptional and cellular changes that enhance clearance of intracellular pathogens at the risk of damaging tissues. IFN-γ effects must therefore be carefully balanced with inhibitory mechanisms to prevent immunopathology. We performed a genome-wide CRISPR knockout screen in a macrophage cell line to identify negative regulators of IFN-γ responses. We discovered an unexpected role of the ubiquitin-fold modifier (Ufm1) conjugation system (herein UFMylation) in inhibiting responses to IFN-γ and lipopolysaccharide. Enhanced IFN-γ activation in UFMylation-deficient cells resulted in increased transcriptional responses to IFN-γ in a manner dependent on endoplasmic reticulum stress responses involving Ern1 and Xbp1. Furthermore, UFMylation in myeloid cells is required for resistance to influenza infection in mice, indicating that this pathway modulates in vivo responses to infection. These findings provide a genetic roadmap for the regulation of responses to a key mediator of cellular immunity and identify a molecular link between the UFMylation pathway and immune responses.

Indexed as

AnimalsAutophagyCell LineChaperone-Mediated AutophagyEndoplasmic ReticulumEndoplasmic Reticulum StressFemaleInterferon-gammaLipopolysaccharidesMacrophage ActivationMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutProtein BindingInterferon-gammaLipopolysaccharidesProteinsUfm1 protein, mouseautophagyER stressimmunologyinterferonUFMylation

Identifiers

PMID33372156
PMCPMC7817147
OpenAlexW3114291139

What OpenQuestion holds

Textmetadata
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.