Evidence map›Paper›PMID 33037057›Full record

ArticleGut2021

Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance.

Dominik Aschenbrenner, Maria Quaranta, Soumya Banerjee, Nicholas Ilott, Joanneke Jansen, Boyd Steere, Yin-Huai Chen, Stephen Ho, Karen Cox, Carolina V Arancibia-Cárcamo and 9 more

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

Article in Gut, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 1 pooled it
4.2field-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

76 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.

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  14. International journal of molecular sciences · 2025
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16 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

19 authors at 7 institutions in 3 countries.

Dominik Aschenbrenner *Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, University of Oxford, Oxford, Oxfordshire, UK.ORCID 0000-0001-7580-2567
Maria Quaranta *Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, University of Oxford, Oxford, Oxfordshire, UK.
Soumya BanerjeeTranslational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, University of Oxford, Oxford, Oxfordshire, UK.ORCID 0000-0001-7748-9885
Nicholas IlottKennedy Institute of Rheumatology, University of Oxford, Oxford, Oxfordshire, UK.
Joanneke JansenTranslational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, University of Oxford, Oxford, Oxfordshire, UK.
Boyd SteereImmunology Translational Sciences, Eli Lilly and Company, Indianapolis, Indiana, USA.
Yin-Huai ChenTranslational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, University of Oxford, Oxford, Oxfordshire, UK.
Stephen HoImmunology Translational Sciences, Eli Lilly and Company, Indianapolis, Indiana, USA.
Karen CoxImmunology Translational Sciences, Eli Lilly and Company, Indianapolis, Indiana, USA.
Carolina V Arancibia-CárcamoTranslational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, University of Oxford, Oxford, Oxfordshire, UK.
Mark ColesKennedy Institute of Rheumatology, University of Oxford, Oxford, Oxfordshire, UK.
Eamonn GaffneyWolfson Centre for Mathematical Biology, University of Oxford, Oxford, Oxfordshire, UK.
Simon Pl TravisTranslational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, University of Oxford, Oxford, Oxfordshire, UK.
Lee DensonPediatric Gastroenterology, Cincinnati Childrens Hospital Medical Center, Cincinnati, Ohio, USA.
Subra KugathasanPediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
Jochen SchmitzImmunology Translational Sciences, Eli Lilly and Company, Indianapolis, Indiana, USA.
Fiona PowrieKennedy Institute of Rheumatology, University of Oxford, Oxford, Oxfordshire, UK.
Stephen N Sansom *Kennedy Institute of Rheumatology, University of Oxford, Oxford, Oxfordshire, UK.
Holm H Uhlig *Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, University of Oxford, Oxford, Oxfordshire, UK holm.uhlig@ndm.ox.ac.uk.ORCID 0000-0002-6111-7355
John Radcliffe Hospital · GBUniversity of Oxford · GBEli Lilly (United States) · USCincinnati Children's Hospital Medical Center · USEmory University · USHumanitas University · ITUniversity of Cambridge · GB

Funding

Wellcome Trust 212240/Z/18/Z
6 · The paper itself

Abstract

objectiveDysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role of interleukin (IL)-23-producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for selective IL-23 targeting therapies as part of personalised medicine.

designWe performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA sequencing to derive a transcriptomic signature of hyperinflammatory monocytes. Using gene network correlation analysis, we deconvolved this signature into components associated with homeostasis and inflammation in patient biopsy samples.

resultsWe characterised monocyte subsets of healthy individuals and patients with IBD that express IL-23. We identified autosensing and paracrine sensing of IL-1α/IL-1β and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion after lipopolysaccharide stimulation, whole bacteria exposure induced IL-23 production in controls via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to antitumour necrosis factor (TNF) therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease.

conclusionOur work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyperinflammation-associated IL-23 production in patients with severe ulcerating active Crohn's disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with IBD that might benefit from IL-23p19 and/or IL-1α/IL-1β-targeting therapies upstream of IL-23.

Indexed as

AdolescentAdultAgedAged, 80 and overAutocrine CommunicationCells, CulturedDrug ResistanceFemaleGene ExpressionGene Expression RegulationGene Regulatory NetworksHomeostasisHumansInflammatory Bowel DiseasesInterleukin-10Interleukin-1alphaIL10 protein, humanIL1A protein, humanIL1B protein, humanIL23A protein, humanInterleukin-10Interleukin-1alphaInterleukin-1betaInterleukin-23 Subunit p19LipopolysaccharidesReceptors, Interleukin-10Tumor Necrosis Factor-alphainflammatory bowel diseaseinterleukinsmucosal immunology

Identifiers

PMID33037057
PMCPMC8108288
OpenAlexW3092258992

What OpenQuestion holds

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LicenceCC BY
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.