Excel · study · 2026
Macrophage VISTA Restrains Inflammatory and Antigen-Presenting Programs During Alloimmune Tissue Injury [RNA-Seq]
Listed in NCBI GEO
Macrophage inflammatory plasticity is a central determinant of immune-mediated tissue injury, yet the intrinsic checkpoint mechanisms that restrain inflammatory macrophage programming remain incompletely defined.
Description
Here, using acute cardiac allograft rejection as an alloimmune tissue-injury model, we found that Vsir, encoding V-domain Ig suppressor of T-cell activation (VISTA), was preferentially expressed in graft macrophages but declined as macrophages acquired inflammatory and antigen-presenting states.
Single-cell RNA sequencing and pseudotime analysis revealed that VISTA downregulation accompanied macrophage progression from reparative/resident-like states toward inflammatory programs. In vitro, VISTA overexpression intrinsically restrained pro-inflammatory macrophage polarization, reduced inflammatory cytokine expression, and limited the induction of antigen-presenting molecules including MHC-II and CD80, thereby attenuating macrophage-driven CD4⁺ T-cell proliferation.
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Integrative CUT&Tag and RNA-seq analyses further showed that VISTA overexpression was associated with reduced H3K4me3 enrichment at inflammatory regulatory loci, including TRAF5 and CHDH, together with transcriptional repression of NF-κB-, TNF-, MAPK-, and IL-17-associated inflammatory programs. In vivo F4/80 promoter-directed Vsir restoration shifted intragraft macrophages away from inflammatory polarization, reduced T-cell accumulation, and attenuated early rejection-associated tissue injury.
Together, these findings identify VISTA as an intrinsic regulator of macrophage inflammatory programming and point to H3K4me3-associated chromatin remodeling as a regulatory layer linked to VISTA-mediated inflammatory restraint.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE338nnn/GSE338333 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE338333 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1493806 ncbi.nlm.nih.gov/bioproject/PRJNA1493806 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Heart 65% · RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 11 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE338333 | 11 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[anatomy].local:anatomy:heart | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:single-cell-rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |