Evidence map›Paper›PMID 25211233›Full record

ArticlePLoS pathogens2014

Incomplete deletion of IL-4Rα by LysM(Cre) reveals distinct subsets of M2 macrophages controlling inflammation and fibrosis in chronic schistosomiasis.

Kevin M Vannella, Luke Barron, Lee A Borthwick, Kristen N Kindrachuk, Prakash Babu Narasimhan, Kevin M Hart, Robert W Thompson, Sandra White, Allen W Cheever, Thirumalai R Ramalingam and 1 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
8.1field-weighted citation impact, top 1% 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

80 citing papers in PubMed, 106 citations in OpenAlex.

  1. Article
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  8. Review
  9. Interstitial macrophage phenotypes inFrontiers in immunology · 2024
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  15. Article
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  18. Macrophages as a therapeutic target to promote diabetic wound healing.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Review
  19. Article
  20. Olfactory receptors contribute to progression of kidney fibrosis.NPJ systems biology and applications · 2022
    Article

20 more citing papers are in PubMed but not listed here.

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

11 authors at 4 institutions in 2 countries.

Kevin M VannellaProgram in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Luke BarronProgram in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Lee A BorthwickProgram in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America; Tissue Fibrosis and Repair Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
Kristen N KindrachukProgram in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Prakash Babu NarasimhanProgram in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Kevin M HartProgram in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Robert W ThompsonProgram in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Sandra WhiteProgram in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Allen W CheeverBiomedical Research Institute, Rockville, Maryland, United States of America.
Thirumalai R RamalingamProgram in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Thomas A WynnProgram in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
National Institutes of Health · USNational Institute of Allergy and Infectious Diseases · USBiomedical Research Institute · USNewcastle University · GB

Funding

Approaches To Immunological Intervention In SchistosomiasisZIAAI000829 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI WYNN, THOMAS · 2009 to 2018
$9.9M
Intramural NIH HHS
6 · The paper itself

Abstract

Mice expressing a Cre recombinase from the lysozyme M-encoding locus (Lyz2) have been widely used to dissect gene function in macrophages and neutrophils. Here, we show that while naïve resident tissue macrophages from IL-4Rαf(lox/delta)LysM(Cre) mice almost completely lose IL-4Rα function, a large fraction of macrophages elicited by sterile inflammatory stimuli, Schistosoma mansoni eggs, or S. mansoni infection, fail to excise Il4rα. These F4/80(hi)CD11b(hi) macrophages, in contrast to resident tissue macrophages, express lower levels of Lyz2 explaining why this population resists LysM(Cre)-mediated deletion. We show that in response to IL-4 and IL-13, Lyz2(lo)IL-4Rα(+) macrophages differentiate into an arginase 1-expressing alternatively-activated macrophage (AAM) population, which slows the development of lethal fibrosis in schistosomiasis. In contrast, we identified Lyz2(hi)IL-4Rα(+) macrophages as the key subset of AAMs mediating the downmodulation of granulomatous inflammation in chronic schistosomiasis. Our observations reveal a limitation on using a LysMCre mouse model to study gene function in inflammatory settings, but we utilize this limitation as a means to demonstrate that distinct populations of alternatively activated macrophages control inflammation and fibrosis in chronic schistosomiasis.

Indexed as

AnimalsCells, CulturedChronic DiseaseCytokinesDisease Models, AnimalFemaleFibrosisInflammationIntegrasesInterleukin-4 Receptor alpha SubunitMacrophages, PeritonealMaleMiceMice, Inbred BALB CNeutrophilsReal-Time Polymerase Chain ReactionCre recombinaseCytokinesIl4ra protein, mouseIntegrasesInterleukin-4 Receptor alpha SubunitReceptors, Cell SurfaceRNA, Messenger

Identifiers

PMID25211233
PMCPMC4161449
OpenAlexW2097592317

What OpenQuestion holds

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LicenceCC0
Read underepoch 390

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.