{"doi":"10.3389/fimmu.2020.580187","title":"VISTA Re-programs Macrophage Biology Through the Combined Regulation of Tolerance and Anti-inflammatory Pathways","abstract":"We present the novel finding that VISTA negatively regulates innate inflammation through the transcriptional and epigenetic re-programming of macrophages. Representative of VISTA re-programming is the ability of VISTA agonistic antibodies to augment LPS tolerance and reduce septic shock lethality in mice. This anti-inflammatory effect of anti-VISTA was mimicked in vitro demonstrating that anti-VISTA treatment caused a significant reduction in LPS-induced IL-12p40, IL-6, CXCL2 and TNF; all hallmark proinflammatory mediators of endotoxin shock. Even under conditions that typically “break” LPS tolerance, VISTA agonists sustained a macrophage anti-inflammatory profile. Analysis of the proteomic and transcriptional changes imposed by anti-VISTA show that macrophage re-programming was mediated by a composite profile of mediators involved in both macrophage tolerance induction (IRG1, miR221, A20, IL-10) as well as transcription factors central to driving an anti-inflammatory profile (e.g. IRF5, IRF8, NFKB1). These findings underscore a novel and new activity of VISTA as a negative checkpoint regulator that induces both tolerance and anti-inflammatory programs in macrophages and controls the magnitude of innate inflammation in vivo.","journal":"Frontiers in Immunology","year":2020,"id":62335,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":52,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9565,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":235906,"name":"Evelien Schaafsma","orcid":"0000-0002-3821-3568","position":1,"is_corresponding":false},{"id":329396,"name":"Nicole C. Smits","orcid":"0000-0002-0059-2646","position":2,"is_corresponding":false},{"id":329397,"name":"Parth Shah","orcid":"0000-0003-2506-9525","position":3,"is_corresponding":false},{"id":363,"name":"Chao Cheng","orcid":"0000-0002-5002-3417","position":4,"is_corresponding":false},{"id":329398,"name":"Christopher M. Burns","orcid":"0000-0001-7144-2752","position":5,"is_corresponding":false},{"id":52067,"name":"Bruce R. Blazar","orcid":"0000-0002-9608-9841","position":6,"is_corresponding":false},{"id":235917,"name":"Randolph J. Noelle","orcid":"0000-0002-2222-2136","position":7,"is_corresponding":false},{"id":330406,"name":"Rodwell Mabaera","orcid":null,"position":8,"is_corresponding":false},{"id":235902,"name":"Mohamed ElTanbouly","orcid":"0000-0001-7985-3839","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-18T21:10:11.612909Z","pmid":"33178206","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}