Evidence map›Paper›PMID 37792013›Full record

ArticleDiabetologia2023

CSF1R inhibition with PLX5622 affects multiple immune cell compartments and induces tissue-specific metabolic effects in lean mice.

Angela J T Bosch, Lena Keller, Laura Steiger, Theresa V Rohm, Sophia J Wiedemann, Andy J Y Low, Marc Stawiski, Leila Rachid, Julien Roux, Daniel Konrad and 6 more

Open access · hybridAbstract read
In one paragraph

Article in Diabetologia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

23 citing papers in PubMed, 27 citations in OpenAlex.

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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

16 authors at 3 institutions in 1 country.

Angela J T BoschDepartment of Biomedicine, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-9895-0850
Lena KellerDepartment of Biomedicine, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-3181-263X
Laura SteigerDepartment of Biomedicine, University of Basel, Basel, Switzerland.
Theresa V RohmDepartment of Biomedicine, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0001-8498-1018
Sophia J WiedemannDepartment of Biomedicine, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-2632-6952
Andy J Y LowDepartment of Biomedicine, University of Basel, Basel, Switzerland.
Marc StawiskiDepartment of Biomedicine, University of Basel, Basel, Switzerland.
Leila RachidDepartment of Biomedicine, University of Basel, Basel, Switzerland.
Julien RouxDepartment of Biomedicine, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-4192-5099
Daniel KonradDivision of Pediatric Endocrinology and Diabetology, University Children's Hospital, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0001-9067-4356
Stephan WueestDivision of Pediatric Endocrinology and Diabetology, University Children's Hospital, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0001-7227-2644
Sonia TuguesInstitute of Experimental Immunology, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-1206-3386
Melanie GreterInstitute of Experimental Immunology, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-7220-5369
Marianne Böni-SchnetzlerDepartment of Biomedicine, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0001-5569-5506
Daniel T MeierDepartment of Biomedicine, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0003-3348-4657
Claudia Cavelti-WederDepartment of Biomedicine, University of Basel, Basel, Switzerland. claudia.cavelti-weder@usz.ch.ORCID http://orcid.org/0000-0002-0650-6091
University of Basel · CHUniversity of Zurich · CHSIB Swiss Institute of Bioinformatics · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aims/hypothesisColony stimulating factor 1 (CSF1) promotes the proliferation, differentiation and survival of macrophages, which have been implicated in both beneficial and detrimental effects on glucose metabolism. However, the physiological role of CSF1 signalling in glucose homeostasis and the potential therapeutic implications of modulating this pathway are not known. We aimed to study the composition of tissue macrophages (and other immune cells) following CSF1 receptor (CSF1R) inhibition and elucidate the metabolic consequences of CSF1R inhibition.

methodsWe assessed immune cell populations in various organs by flow cytometry, and tissue-specific metabolic effects by hyperinsulinaemic-euglycaemic clamps and insulin secretion assays in mice fed a chow diet containing PLX5622 (a CSF1R inhibitor) or a control diet.

resultsCSF1R inhibition depleted macrophages in multiple tissues while simultaneously increasing eosinophils and group 2 innate lymphoid cells. These immunological changes were consistent across different organs and were sex independent and reversible after cessation of the PLX5622. CSF1R inhibition improved hepatic insulin sensitivity but concomitantly impaired insulin secretion. In healthy islets, we found a high frequency of IL-1β CONCLUSIONS/

interpretationMacrophages and macrophage-derived factors, such as IL-1β, play an important role in physiological insulin secretion. A better understanding of the tissue-specific effects of CSF1R inhibition on immune cells and glucose homeostasis is crucial for the development of targeted immune-modulatory treatments in metabolic disease. DATA AVAILABILITY: The RNA-Seq dataset is available in the Gene Expression Omnibus (GEO) under the accession number GSE189434 ( http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE189434 ).

Indexed as

Immunity, InnateLymphocytesAnimalsGlucoseMacrophagesMiceOrganic ChemicalsGlucoseOrganic ChemicalsPLX5622Colony stimulating factor 1 (CSF1)EosinophilsIL-1βInnate lymphoid cellsInsulin secretionInsulin sensitivityMacrophagesPLX5622

Identifiers

PMID37792013
PMCPMC10627931
OpenAlexW4387326314

What OpenQuestion holds

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LicenceCC BY
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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.