{"doi":"10.17615/1a9k-7q83","title":"Towards programming immune tolerance through geometric manipulation of phosphatidylserine","abstract":"The possibility of engineering the immune system in a targeted fashion using biomaterials such as nanoparticles has made considerable headway in recent years. However, little is known as to how modulating the spatial presentation of a ligand augments downstream immune responses. In this report we show that geometric manipulation of phosphatidylserine (PS) through fabrication on rod-shaped PLGA nanoparticles robustly dampens inflammatory responses from innate immune cells while promoting T regulatory cell abundance by impeding effector T cell expansion. This response depends on the geometry of PS presentation as both PS liposomes and 1 micron cylindrical PS-PLGA particles are less potent signal inducers than 80 × 320 nm rod-shaped PS-PLGA particles for an equivalent dose of PS. We show that this immune tolerizing effect can be co-opted for therapeutic benefit in a mouse model of multiple sclerosis and an assay of organ rejection using a mixed lymphocyte reaction with primary human immune cells. These data provide evidence that geometric manipulation of a ligand via biomaterials may enable more efficient and tunable programming of cellular signaling networks for therapeutic benefit in a variety of disease states, including autoimmunity and organ rejection, and thus should be an active area of further research.","journal":"UNC Libraries","year":2020,"id":137978,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"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":599364,"name":"Reid A. Roberts","orcid":null,"position":1,"is_corresponding":false},{"id":225654,"name":"Jenny P.‐Y. Ting","orcid":"0000-0002-3282-419X","position":2,"is_corresponding":false},{"id":371630,"name":"Joseph M. DeSimone","orcid":"0000-0001-9521-5095","position":3,"is_corresponding":false},{"id":549149,"name":"Shannon Reisdorf","orcid":null,"position":4,"is_corresponding":false},{"id":598684,"name":"Patrick Short","orcid":"0000-0002-7626-6177","position":5,"is_corresponding":false},{"id":591952,"name":"Timothy K. Eitas","orcid":"0009-0000-5953-1306","position":6,"is_corresponding":false},{"id":371631,"name":"James D. Byrne","orcid":"0000-0002-6436-2866","position":7,"is_corresponding":false},{"id":598685,"name":"Brandon M. Johnson","orcid":"0000-0002-3871-3378","position":8,"is_corresponding":false},{"id":432365,"name":"J. Christopher Luft","orcid":"0000-0003-2042-7397","position":9,"is_corresponding":false},{"id":408425,"name":"Karen P. McKinnon","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:59.449905Z","pmid":null,"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":[]}