{"doi":"10.1073/pnas.2409852122","title":"Engineered immunological niche directs therapeutic development in models of progressive multiple sclerosis","abstract":"Primary progressive multiple sclerosis (MS) is a demyelinating autoimmune disease with only a single class of FDA-approved treatment, B cell depletion. Novel treatments could emerge from a deeper understanding of the interplay between multiple cell types within diseased tissue throughout progression. We initially describe an engineered biomaterial-based immunological niche (IN) as a surrogate for diseased tissue to investigate immune cell function and phenotype dynamics throughout a chronic progressive mouse model of MS. Using these niches, we identify an array of dysregulated CC chemokine signaling as potential targets. We then develop antigen-loaded nanoparticles that reduce CC chemokine signaling, while delivering antigen. These nanoparticles serve as an antigen-specific treatment, and a single injection reduces disease burden, even if administered after symptomatic disease onset. This report demonstrates proof of principle of a biomaterial scaffold as a diseased tissue surrogate that can monitor immune function, identify potential drug targets, and guide the development of a therapeutic.","journal":"Proceedings of the National Academy of Sciences","year":2025,"id":530409,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9527,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":369754,"name":"Kevin R. Hughes","orcid":"0000-0002-1706-2799","position":1,"is_corresponding":false},{"id":1410121,"name":"Sydney N. Wheeler","orcid":"0009-0008-8221-5449","position":2,"is_corresponding":false},{"id":505302,"name":"Joseph T. Decker","orcid":"0000-0001-7914-4741","position":3,"is_corresponding":false},{"id":388295,"name":"Sophia M. Orbach","orcid":"0000-0002-1852-6890","position":4,"is_corresponding":false},{"id":1056393,"name":"Angelica Rose Galvan","orcid":"0000-0002-7616-4760","position":5,"is_corresponding":false},{"id":1410453,"name":"Jasmine Thornhill","orcid":null,"position":6,"is_corresponding":false},{"id":783925,"name":"Kate Griffin","orcid":"0000-0002-8644-7780","position":7,"is_corresponding":false},{"id":885177,"name":"Hamza Turkistani","orcid":null,"position":8,"is_corresponding":false},{"id":437526,"name":"Russell Urie","orcid":"0000-0002-2728-2541","position":9,"is_corresponding":false},{"id":369756,"name":"David N. Irani","orcid":"0000-0002-3634-1742","position":10,"is_corresponding":false},{"id":260792,"name":"Lonnie D. Shea","orcid":"0000-0002-9296-9673","position":11,"is_corresponding":false},{"id":369753,"name":"Aaron H. Morris","orcid":"0000-0002-4680-2493","position":12,"is_corresponding":false},{"id":701606,"name":"Laila M. Rad","orcid":"0000-0001-7965-7272","position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":null,"created_at":"2026-07-19T02:51:05.836974Z","pmid":"39937858","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":[]}