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Omics · study · 2026

Intestine epithelial Ceacam1 deficiency prevents steroid-refractory acute gut graft-versus-host disease

Listed in NCBI GEO

Steroid refractory gut acute graft-versus-host disease (SR-Gut-aGVHD) is the major cause of non-relapse death after allogeneic hematopoietic cell transplantation, due to poor understanding its pathogenesis.

Description

We recently reported that increase of donor-type IL-22+ T cells, IL-22-dependent dysbiosis, and loss of anti-inflammatory CX3CR1hi mononuclear phagocytes (MNP) play critical roles in SR-Gut-aGVHD pathogenesis, but the mechanisms remain unclear.

Ceacam1 on intestinal epithelial cells (IECs) is proposed to regulate bacterial translocation and subsequent immune response in the gut tissues. Here, with imaging mass cytomtory (IMC), combined scRNA-Seq and ATAC-Seq, as well as high dimensional flow cytometry analysis, we show that Ceacam1 expression is enhanced on IECs in murine and human SR-Gut-aGVHD. Ceacam1 deficiency on host IECs effectively prevents SR-Gut-aGVHD in murine models.

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Ceacam1 deficiency on IECs results in 1) increase in frequencies of IL-22+IL-10+Foxp3+CD4+ peripheral Tregs (pTregs) while reducing conventional IL-22+CD4+ T (Tcon), Th/Tc1, and Th17 cells; 2) increase of beneficial commensal bacterial that augment colonic pTregs expansion, while reducing pathogenic bacteria and blocking E. Coli’s interaction with IECs; and 3) increase of anti-inflammatory CD103-CX3CR1hi MNP that produce IDO and IL-10, while reducing pro-inflammatory CD103+CX3CR1lo MNP that produce IL-6.

Thus, specific targeting IEC Ceacam1 represents a novel approach for prevention of SR-Gut-aGVHD.

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From keywords
Life Sciences
Inferred from text
Disease 75% · Imaging 75% · Single-cell RNA sequencing 65%
Provenance · 1 source records, 11 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE26899315 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:diseaseenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:imagingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:single-cell-rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title