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Granzyme K CD8⁺ T cells with tissue-resident features promote intestinal inflammation in patients with Crohn’s disease

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Dataset overview

Participants 2
Samples 45
Reuse readiness 8.1/10 evidence-backed score

Granzyme K CD8⁺ T cells with tissue-resident features promote intestinal inflammation in patients with Crohn's disease.

Lee Y, Kim TY, Kim Y, Baek J, Park H, Yoon DK, Hwang SW, Lee JL, et al. · Experimental & molecular medicine · 2026

Abstract

The role of CD8<sup>+</sup> T cells in Crohn's disease (CD) pathogenesis remains incompletely understood. This study aimed to characterize CD8<sup>+</sup> T cells in CD and elucidate their potential contribution to intestinal inflammation. T cells from blood and intestinal tissues of 15 patients with CD were analyzed using single-cell RNA and T cell receptor sequencing. Spatial transcriptomics was conducted on inflamed intestinal tissues from two patients. Analysis of 41,699 CD8<sup>+</sup> T cells identified distinct subsets characterized by differential granzyme expression: granzyme B (GZMB<sup>+</sup>) CD8<sup>+</sup> T cells, predominantly in blood with high cytotoxic potential, and granzyme K (GZMK<sup>+</sup>) CD8<sup>+</sup> T cells, enriched in intestinal tissue with lower cytotoxic potential. In the small intestine, GZMK<sup>+</sup>CD8<sup>+</sup> T cells displayed enhanced tissue residency signatures (for example, CXCR6) and downregulated egress-related genes (S1PR1and S1PR5). GZMK<sup>+</sup>CD8<sup>+</sup> T cells displayed robust interactions with myeloid cells via the CXCR3-CXCL9/10 axis, coupled with notable colocalization in the small intestine. Pharmacological inhibition of GZMK alleviated intestinal inflammation and tissue damage in a murine model of intestinal injury, supporting its role in modulating inflammatory responses. Together, these findings highlight GZMK as a potential modulator of intestinal inflammation and a candidate for further therapeutic investigation.

doi:10.1038/s12276-026-01763-7 ↗ PMID 42409960 ↗ PMC13434261 ↗

Study facts

Organism
Homo sapiens
Platform
10x Genomics Visium and 10x Genomics Xenium
Age group
—
Disease groups
Crohn's disease
Anatomical sites
Lamina propria of the uninflamed small intestine, Submucosa of the uninflamed small intestine, Blood, Inflamed small intestine, Uninflamed small intestine, 10 µm section Inflamed small intestine

Data availability

  • Raw counts
  • Processed matrix
  • Spatial coordinates
  • Histology images
  • Analysis code

File types CSVJPGJSONMTXPNGTIFFTSV

Strengths & limitations for reuse

Strengths

  • Raw counts are advertised
  • Processed matrices are advertised
  • Spatial coordinates are advertised
  • Histology images are advertised
  • Analysis code is available
  • Participant counts are documented
Extraction evidence & provenance

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

Assay

FieldValueEvidence
assay.panel_size 475
A list of the 475 predesigned genes used for 10× Xenium analysis is provided in Supplementary Table 4.

Section Materials and methods — ST using 10× Xenium, offset 11150
assay.platform 10x Genomics Visium and 10x Genomics Xenium
An inflamed intestinal tissue obtained from a patient with CD was processed for 10x visium spatial transcriptomic analysis. An inflamed intestinal tissue obtained from a patient with CD was processed for 10x xenium spatial transcriptomic analysis.

Section series_overall_design; samples[GSM8795105]; samples[GSM8803514], offset —
assay.platform_version Visium spatial 3′ v2
Data were aligned to the hg38 reference genome and normalized using Space Ranger (10X Genomics, spatial 3′ v2; spaceranger-2.1.0).

Section samples[GSM8795105].data_processing, offset —
assay.reference_genome GRCh38 from source
GRCh38

Section GEO family SOFT, offset —
assay.resolution spot
Inflamed small intestine, Crohn's disease [10x visium spatial transcriptomics]

Section samples[GSM8795105].supplementary_files; samples[GSM8795105].title, offset —
assay.segmentation_method XeniumRanger v1.7.1
Raw data were preprocessed with XeniumRanger v1.7.1 (10x Genomics)

Section Sample GSM8803514 — data_processing, offset 900
assay.sequencing_based True from source
GEO assay type/library strategy: OTHER, RNA-SEQ

Section GEO family SOFT, offset —
assay.whole_transcriptome True from source
GEO library strategy=['OTHER', 'RNA-SEQ']

Section GEO family SOFT, offset —

Cohort

FieldValueEvidence
cohort.crohns_disease_participants 2
Spatial transcriptomics was conducted on inflamed intestinal tissues from two patients.

Section abstractText, offset 6500
cohort.total_participants 2
Spatial transcriptomics was conducted on inflamed intestinal tissues from two patients.

Section abstractText, offset 6500

Data_Assets

FieldValueEvidence
data_assets.analysis_code True from source
GEO deposit evidence: ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM8792nnn/GSM8792736/suppl/GSM8792736_CD1_1_Uninf_barcodes.tsv.gz

Section GEO family SOFT, offset —
data_assets.file_manifest True from source
Supplementary files enumerated in family SOFT (ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM8792nnn/GSM8792736/suppl/GSM8792736_CD1_1_Uninf_barcodes.tsv.gz, ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM8795nnn/GSM8795105/suppl/GSM8795105_CD16_Inf_tissue_hires_image.png.gz, ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM8795nnn/GSM8795105/suppl/GSM8795105_CD16_Inf_tissue_positions.csv.gz)

Section GEO family SOFT, offset —
data_assets.histology_images True from source
GEO deposit evidence: ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM8795nnn/GSM8795105/suppl/GSM8795105_CD16_Inf_tissue_hires_image.png.gz

Section GEO family SOFT, offset —
data_assets.open_access True from source
Public on Jul 01 2026

Section series_status, offset —
data_assets.participant_metadata True
"subject status": "a patient with CD"

Section Sample GSM8795105 — characteristics, offset 600
data_assets.processed_matrix True
CD16_Inf_matrix.mtx.gz: gene expression count data in Matrix Market Exchange Format

Section Sample GSM8795105 — supplementary files, offset 1700
data_assets.raw_counts True from source
GEO deposit evidence: MTX in GEO suppfile types

Section GEO record summary, offset —
data_assets.sample_metadata True
Inflamed small intestine, Crohn's disease [10x visium spatial transcriptomics]

Section samples[GSM8795105]; samples[GSM8803514], offset —
data_assets.spatial_coordinates True from source
GEO deposit evidence: ftp://ftp.ncbi.nlm.nih.gov/geo/samples/GSM8795nnn/GSM8795105/suppl/GSM8795105_CD16_Inf_tissue_positions.csv.gz

Section GEO family SOFT, offset —

Specimens

FieldValueEvidence
specimens.anatomical_sites ['Lamina propria of the uninflamed small intestine', 'Submucosa of the uninflamed small intestine', 'Blood', 'Inflamed small intestine', 'Uninflamed small intestine', '10 µm section Inflamed small intestine'] from source
GEO sample source names: Lamina propria of the uninflamed small intestine; Submucosa of the uninflamed small intestine; Blood; Inflamed small intestine; Uninflamed small intestine; 10 µm section Inflamed small intestine

Section GEO family SOFT, offset —
specimens.inflamed_status_available True from source
GEO sample characteristics report inflammation status

Section GEO family SOFT, offset —
specimens.number_of_samples 45 computed
45 GSM records parsed from GEO family SOFT

Section GEO family SOFT, offset —
specimens.preservation_method OCT-embedded frozen tissue
An inflamed OCT-embedded frozen small intestinal tissue block from a patient with CD was processed for 10x Visium analysis.

Section samples[GSM8795105].extract_protocol, offset —