DOP45 Blood-derived neutrophils give rise to differentially activated populations in the mucosa of active Inflammatory Bowel Disease patients Article Swipe
Marisol Veny
,
Ángela Sanzo-Machuca
,
A M Corraliza
,
Floortje Strobbe
,
Alba Garrido-Trigo
,
Victòria Gudiño
,
E Melón-Ardanaz
,
Míriam Esteller
,
Iris Teubel
,
Maria Carme Masamunt
,
Íngrid Ordás
,
Cristina Prieto
,
À Giner
,
Albert Martín‐Cardona
,
María Esteve
,
E Ricart
,
Azucena Salas
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1093/ecco-jcc/jjad212.0085
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1093/ecco-jcc/jjad212.0085
Background Infiltration of neutrophils is the main histological feature in active inflammatory bowel disease (IBD). Recent data suggests that tissue- and tumour-infiltrating neutrophils can adopt remarkably different phenotypes with potentially different functions. However, the heterogeneity of this population in IBD remains unknown. Methods Single-cell RNA sequencing (scRNA-seq) data was generated from colonic biopsies of 92 individuals including 6 healthy controls (HC), 36 inactive IBD, 19 active Crohn’s disease (CD) and 31 active ulcerative colitis (UC) patients. Neutrophils (6038 cells) found in the inflamed colon of CD and UC patients were analysed using a curated pipeline in Seurat (v4.0.2)1. Posterior analysis included the FindAllMarkers function (differentially expressed genes), Jaccard index similarity and the AddModuleScore function (comparisons with literature-described neutrophils), Monocle3 algorithm (developmental trajectory) and clusterProfiler (v3.0.4; enrichment and pathway analysis). For in vitro stimulation, neutrophils were isolated from the blood of HC donors (n=4) using a double Ficoll gradient 1. Cells and supernatants were analysed for qPCR and ELISA determinations. Results We identified 6 different clusters/states of colonic neutrophils (Figure 1A). In agreement with our previous results1 we found a population of S100A12/S100A8/S100A9 neutrophils (N0), IFN-response neutrophils (N3) and CCL3/CCL4 neutrophils (N2), in addition to N1.1 and N1.2 neutrophils. N3 neutrophils were enriched in the inflamed colon of CD patients compared to UC (17.2% vs 5.8%, p-value= 0.0021; Figure 1C). Comparative analysis with published datasets revealed that N0, N1.2 and N3 resemble populations of neutrophils found in blood2,3. In contrast, N1.1 and N2-like clusters showed some similarity to umbilical cord blood3 and tumour-infiltrating neutrophils4. Trajectory analysis, originating from N0 (peripheral-like) neutrophils, showed two potential branches of differentiation, with N1.2 leading towards N3 (IFN-response) and N1.1 differentiating into N2 (CCL3) neutrophils (Figure 1B). Finally, pathway analysis showed that N2 neutrophils presented enriched gene expression of the TNF signalling pathway, and together with the N1.1 state, an enrichment of the IL1β signalling pathway as well. In vitro experiments revealed that TNF, IL1β and LPS can all induce expression of CCL3 and CCL4, top differentially expressed genes of N2 neutrophils. Conclusion We show that active IBD is associated with a highly heterogeneous population of infiltrating neutrophils. Some of them resemble neutrophils in peripheral blood, while others most likely differentiate in response to inflammatory cues present in the colon of active IBD patients.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/ecco-jcc/jjad212.0085
- https://academic.oup.com/ecco-jcc/article-pdf/18/Supplement_1/i154/56348118/jjad212.0085.pdf
- OA Status
- bronze
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4391162906
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- OpenAlex ID
-
https://openalex.org/W4391162906Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1093/ecco-jcc/jjad212.0085Digital Object Identifier
- Title
-
DOP45 Blood-derived neutrophils give rise to differentially activated populations in the mucosa of active Inflammatory Bowel Disease patientsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
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2024Year of publication
- Publication date
-
2024-01-01Full publication date if available
- Authors
-
Marisol Veny, Ángela Sanzo-Machuca, A M Corraliza, Floortje Strobbe, Alba Garrido-Trigo, Victòria Gudiño, E Melón-Ardanaz, Míriam Esteller, Iris Teubel, Maria Carme Masamunt, Íngrid Ordás, Cristina Prieto, À Giner, Albert Martín‐Cardona, María Esteve, E Ricart, Azucena SalasList of authors in order
- Landing page
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https://doi.org/10.1093/ecco-jcc/jjad212.0085Publisher landing page
- PDF URL
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https://academic.oup.com/ecco-jcc/article-pdf/18/Supplement_1/i154/56348118/jjad212.0085.pdfDirect link to full text PDF
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YesWhether a free full text is available
- OA status
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bronzeOpen access status per OpenAlex
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https://academic.oup.com/ecco-jcc/article-pdf/18/Supplement_1/i154/56348118/jjad212.0085.pdfDirect OA link when available
- Concepts
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Inflammatory bowel disease, Medicine, Ulcerative colitis, Immunology, Population, Colitis, S100A8, Transcriptome, Crohn's disease, Inflammation, Pathology, Gene, Gene expression, Disease, Biology, Environmental health, BiochemistryTop concepts (fields/topics) attached by OpenAlex
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0Total citation count in OpenAlex
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10Other works algorithmically related by OpenAlex
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