Evidence map›Paper›PMID 34887405›Full record

ArticleNature communications2021

CRIg on liver macrophages clears pathobionts and protects against alcoholic liver disease.

Yi Duan, Huikuan Chu, Katharina Brandl, Lu Jiang, Suling Zeng, Nairika Meshgin, Eleni Papachristoforou, Josepmaria Argemi, Beatriz G Mendes, Yanhan Wang and 13 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
6.4field-weighted citation impact, top 2% 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

56 citing papers in PubMed, 68 citations in OpenAlex.

  1. Article
  2. Article
  3. Therapeutics for Alcohol-Associated Liver Disease.Annual review of pharmacology and toxicology · 2026
    Review
  4. Adoptive transfer of VSIG4Journal of translational medicine · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Myeloid cells in chronic liver inflammation.Cellular & molecular immunology · 2025
    Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. 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

23 authors at 3 institutions in 4 countries.

Yi Duan *Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Huikuan Chu *Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Katharina BrandlSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Lu JiangDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Suling ZengDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Nairika MeshginDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Eleni PapachristoforouUniversity of Edinburgh Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, UK.ORCID http://orcid.org/0000-0003-1553-1405
Josepmaria ArgemiDivision of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh Liver Research Center, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-1696-7753
Beatriz G MendesDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Yanhan WangDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Hua SuLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Weizhong SunDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Cristina LlorenteDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-8135-9186
Tim HendrikxDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Xiao LiuDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Mojgan HosseiniDepartment of Pathology, University of California San Diego, La Jolla, CA, USA.
Tatiana KisselevaDepartment of Surgery, University of California San Diego, La Jolla, CA, USA.
David A BrennerDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Ramon BatallerDivision of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh Liver Research Center, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-1119-7799
Prakash RamachandranUniversity of Edinburgh Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, UK.ORCID http://orcid.org/0000-0001-5996-2413
Michael KarinLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Wenxian FuDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Bernd SchnablDepartment of Medicine, University of California San Diego, La Jolla, CA, USA. beschnabl@ucsd.edu.ORCID http://orcid.org/0000-0002-6281-825X
University of California San Diego · USCentre for Inflammation Research · GBUniversity of Pittsburgh Medical Center · US

Funding

The Southernearch Center for ALPD and CirrhosisP50AA011999 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ANNA S. GUKOVSKAYA · 1999 to 2026
$45.8M
USC RESEARCH CENTER FOR LIVER DISEASES: PILOT PROGRAMSP30DK048522 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KAPLOWITZ, NEIL · 1995 to 2020
$21.8M
San Diego Digestive Diseases Research CenterP30DK120515 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bernd G. Schnabl · 2019 to 2026
$10.8M
Clinical Resources for Alcoholic Hepatitis InvestigationsR24AA025017 · NIAAA · JOHNS HOPKINS UNIVERSITY · PI ZHAOLI SUN · 2016 to 2026
$6.6M
NF-kappaB and Mitochondrial Signals as Positive and Negative Regulators of InflammationR37AI043477 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Karin · 2018 to 2026
$6.0M
Inactivation of Hepatic Stellate Cells During Reversal of Liver FibrosisR01DK099205 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRENNER, DAVID A., KISSELEVA, TATIANA · 2014 to 2025
$4.8M
The Role of the Intestinal Mycobiome in Alcoholic Liver DiseaseR01AA024726 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bernd G. Schnabl · 2018 to 2026
$3.9M
The Role of Portal Fibroblasts in Cholestatic Liver FibrosisR01DK101737 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KISSELEVA, TATIANA · 2014 to 2025
$3.8M
Novel IL-23 inhibitor for the treatment of alcohol associated liver diseaseU01AA029019 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KISSELEVA, TATIANA, LOOMBA, ROHIT · 2020 to 2024
$3.7M
Immunosuppressive mechanisms responsible for development of non-viral liver cancer and control of its response to immune checkpoint inhibitorsU01AA027681 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI EL-KHOUEIRY, ANTHONY BOUTROS, KARIN, MICHAEL · 2018 to 2022
$3.6M
Microbiome and Intestinal Innate Immune Response in Alcoholic Liver DiseaseR37AA020703 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bernd G. Schnabl · 2021 to 2026
$2.5M
The role of IL-17 signaling in alcohol-induced HCCR01AA028550 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRENNER, DAVID A., KISSELEVA, TATIANA · 2021 to 2025
$2.3M
BLRD VA I01 BX004594Medical Research Council MR/N008340/1NIAAA NIH HHS P50 AA011999NIAAA NIH HHS R01 AA024726NIAAA NIH HHS R01 AA028550NIAAA NIH HHS R24 AA025017NIAAA NIH HHS R37 AA020703NIAAA NIH HHS U01 AA026939NIAAA NIH HHS U01 AA026972NIAAA NIH HHS U01 AA027681NIAAA NIH HHS U01 AA029019NIAID NIH HHS R37 AI043477NIDDK NIH HHS P30 DK048522NIDDK NIH HHS P30 DK120515NIDDK NIH HHS R01 DK099205NIDDK NIH HHS R01 DK101737NIDDK NIH HHS R01 DK111866NIMH NIH HHS F31 MH083401
6 · The paper itself

Abstract

Complement receptor of immunoglobulin superfamily (CRIg) is expressed on liver macrophages and directly binds complement component C3b or Gram-positive bacteria to mediate phagocytosis. CRIg plays important roles in several immune-mediated diseases, but it is not clear how its pathogen recognition and phagocytic functions maintain homeostasis and prevent disease. We previously associated cytolysin-positive Enterococcus faecalis with severity of alcohol-related liver disease. Here, we demonstrate that CRIg is reduced in liver tissues from patients with alcohol-related liver disease. CRIg-deficient mice developed more severe ethanol-induced liver disease than wild-type mice; disease severity was reduced with loss of toll-like receptor 2. CRIg-deficient mice were less efficient than wild-type mice at clearing Gram-positive bacteria such as Enterococcus faecalis that had translocated from gut to liver. Administration of the soluble extracellular domain CRIg-Ig protein protected mice from ethanol-induced steatohepatitis. Our findings indicate that ethanol impairs hepatic clearance of translocated pathobionts, via decreased hepatic CRIg, which facilitates progression of liver disease.

Indexed as

AnimalsBacterial TranslocationComplement C3bEnterococcus faecalisEthanolFemaleGastrointestinal TractGram-Positive Bacterial InfectionsHumansLiverLiver Diseases, AlcoholicMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutComplement C3bCR1 protein, humanEthanolReceptors, ComplementReceptors, Complement 3bVSIG4 protein, mouse

Identifiers

PMID34887405
PMCPMC8660815
OpenAlexW4200495156

What OpenQuestion holds

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Registered trials

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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.