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Systemic reprogramming of monocytes in Crohn’s disease promotes their intestinal inflammatory function

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Dataset overview

Participants 20
Samples 20
Reuse readiness 7.7/10 evidence-backed score

Systemic reprogramming of monocytes in Crohn's disease promotes their intestinal inflammatory function.

Hornsby E, Gadhok R, Hoti I, Wozniak E, Boot JR, Connick E, Stevens P, Creed H, et al. · JCI insight · 2026

Abstract

Bone marrow-derived circulating monocytes continuously replenish intestinal macrophages, which become dysregulated in inflammatory bowel disease (IBD) and contribute to disease pathology. The origins of this dysregulation remain poorly understood. Here, we investigate the reprogramming of circulating monocytes in IBD prior to tissue recruitment using single-cell transcriptomic, epigenomic, and functional approaches. We characterize blood monocyte heterogeneity in newly diagnosed, treatment-naive IBD patients and healthy controls and show that monocytes in Crohn's disease (CD) display a distinct transcriptional profile and altered distributions across inferred developmental trajectories; less pronounced changes were observed in ulcerative colitis (UC). We link CD-associated transcriptional changes to alterations in chromatin accessibility and identify NF-κB, EGR, KLF, and AP-1 family transcription factors as putative regulators of an inflammatory gene program in blood monocytes from patients with CD. We uncover a potential role for IFN-γ in priming blood monocytes for inflammatory function in CD by limiting their capacity to be regulated by IL-10. Finally, we show that the transcriptional and functional alterations in monocytes from patients with CD are maintained in monocyte-derived cells from the intestine. Together these data suggest that intestinal macrophage dysfunction in CD is, at least in part, pre-established by systemic signals prior to tissue recruitment.

doi:10.1172/jci.insight.192830 ↗ PMID 42579564 ↗ PMC13596727 ↗

Study facts

Organism
Homo sapiens
Platform
10x Genomics Chromium 3′ assay; Illumina NovaSeq 6000
Age group
adult
Disease groups
—
Anatomical sites
peripheral blood

Data availability

  • Raw counts
  • Processed matrix

File types MTXTSV

Strengths & limitations for reuse

Strengths

  • Raw reads are advertised
  • Raw counts are advertised
  • Processed matrices are advertised
  • Participant counts are documented

Limitations

  • Not documented: cell metadata are advertised
Extraction evidence & provenance

Each extracted field is shown with the source excerpt and location used to resolve it.

Assay

FieldValueEvidence
assay.assay_type single-cell RNA sequencing of total monocytes
scRNAseq was performed on total monocytes isolated by negative magnetic selection

Section series_overall_design, offset —
assay.library_chemistry 10x Genomics Chromium Single Cell 3′ Gel Beads-in-Emulsion, Library and Gel Bead Kit v3
Chromium Single Cell 3′ Gel Beads-in-Emulsion (GEM), Library and Gel Bead Kit v3

Section Methods — scRNA library preparation and sequencing of blood monocytes., offset —
assay.platform 10x Genomics Chromium 3′ assay; Illumina NovaSeq 6000
using the 10x Genomics Chromium 3′ assay

Section series_overall_design, offset —
assay.reference_genome GRCh38 GENCODE v2/Ensembl 98
Assembly: GRCh38 GENCODE v2/ Ensembl 98

Section data_processing, offset —
assay.sequencing_type scrna_seq
scRNA library preparation and sequencing of blood monocytes

Section Methods — scRNA library preparation and sequencing of blood monocytes., offset —

Cohort

FieldValueEvidence
cohort.age_group adult
Adult

Section MeSH headings, offset —
cohort.crohns_disease_participants 6
12 patients with newly diagnosed IBD (CD, n = 6; UC, n = 6)

Section Results — Circulating monocytes exhibit heterogeneity in health and IBD., offset —
cohort.disease_activity_metadata_available True
12 newly diagnosed, treatment naive IBD patients with active endoscopic disease

Section series_overall_design, offset —
cohort.non_ibd_controls 8
and 8 age-, ethnicity-, and sex-matched HCs

Section Results — Circulating monocytes exhibit heterogeneity in health and IBD., offset —
cohort.total_participants 20
scRNA-seq on monocytes enriched from the peripheral blood of 12 patients with newly diagnosed IBD (CD, n = 6; UC, n = 6) and 8 age-, ethnicity-, and sex-matched HCs

Section Results — Circulating monocytes exhibit heterogeneity in health and IBD., offset —
cohort.treatment_exposure_documented True
newly diagnosed, treatment-naive CD and UC patients

Section Results — Circulating monocytes exhibit heterogeneity in health and IBD., offset —
cohort.ulcerative_colitis_participants 6
12 patients with newly diagnosed IBD (CD, n = 6; UC, n = 6)

Section Results — Circulating monocytes exhibit heterogeneity in health and IBD., offset —

Data_Assets

FieldValueEvidence
data_assets.open_access True
"isOpenAccess": "Y"

Section publication metadata, offset —
data_assets.processed_matrix True
"suppfile": "MTX, TSV"

Section geo_record_summary, offset —
data_assets.raw_counts True
_matrix.mtx.gz

Section supplementary_files, offset —
data_assets.raw_reads True
GSE268626_RAW.tar

Section series_supplementary_file, offset —

Processing

FieldValueEvidence
processing.batch_correction_reported True
integrated samples by canonical correlation analysis (CCA)

Section Methods — scRNA-seq data analysis of blood monocytes., offset —
processing.cell_type_annotation_method Graph-based clustering and marker-gene expression
graph-based clustering identified 5 transcriptionally distinct monocyte clusters

Section Results — Circulating monocytes exhibit heterogeneity in health and IBD., offset —
processing.normalization_method Log normalization
We performed log normalization

Section Methods — scRNA-seq data analysis of blood monocytes., offset —
processing.quality_control_reported True
cells with mitochondrial percentages greater than 25 and unique feature counts of less than 1,000 and greater than 5,000 were filtered out

Section Methods — scRNA-seq data analysis of blood monocytes., offset —

Specimens

FieldValueEvidence
specimens.anatomical_sites ['peripheral blood']
scRNAseq was performed on total monocytes isolated by negative magnetic selection from the peripheral blood

Section series_overall_design, offset —
specimens.number_of_cells 19967
a single object of 19,967 cells derived from both patients with IBD and HCs

Section Results — Circulating monocytes exhibit heterogeneity in health and IBD., offset —
specimens.number_of_samples 20
"sample_count": 20

Section dataset authority, offset —