{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE338nnn/GSE338267/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE338267"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Macrophage VISTA Restrains Inflammatory and Antigen-Presenting Programs During Alloimmune Tissue Injury","description":"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. 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. 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.","dates":{"publication":"2026/08/01"},"accession":"GSE338267","cross_references":{"GSM":["GSM9870367","GSM9870366","GSM9870369","GSM9870368"],"GPL":["24247"],"GSE":["338267"],"taxon":["Mus musculus"]}}