{"doi":"10.3390/ijms24098000","title":"Defective Induction of IL-27-Mediated Immunoregulation by Myeloid DCs in Multiple Sclerosis","abstract":"The purpose of this study was to examine whether myeloid dendritic cells (mDCs) from patients with multiple sclerosis (MS) and healthy controls (HCs) become similarly tolerogenic when exposed to IL-27 as this may represent a potential mechanism of autoimmune dysregulation. Our study focused on natural mDCs that were isolated from HCs and MS patient peripheral blood mononuclear cells (PBMCs). After a 24-h treatment with IL-27 ± lipopolysaccharide (LPS), the mDCs were either harvested to identify IL-27-regulated gene expression or co-cultured with naive T-cells to measure how the treated DC affected T-cell proliferation and cytokine secretion. mDCs isolated from HCs but not untreated MS patients became functionally tolerogenic after IL-27 treatment. Although IL-27 induced both HC and untreated MS mDCs to produce similar amounts of IL-10, the tolerogenic HC mDCs expressed PD-L2, IDO1, and SOCS1, while the non-tolerogenic untreated MS mDCs expressed IDO1 and IL-6R. Cytokine and RNA analyses identified two signature blocks: the first identified genes associated with mDC tolerizing responses to IL-27, while the second was associated with the presence of MS. In contrast to mDCs from untreated MS patients, mDCs from HCs and IFNb-treated MS patients became tolerogenic in response to IL-27. The genes differentially expressed in the different donor IL-27-treated mDCs may contain targets that regulate mDC tolerogenic responses.","journal":"International Journal of Molecular Sciences","year":2023,"id":368567,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9641,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":3256,"name":"Nathalie Pochet","orcid":"0000-0003-1820-5656","position":1,"is_corresponding":false},{"id":328225,"name":"Bibek R. Thapa","orcid":"0000-0001-5254-0808","position":2,"is_corresponding":false},{"id":630815,"name":"Radhika Raheja","orcid":"0000-0003-3372-0664","position":3,"is_corresponding":false},{"id":1126903,"name":"Maria Antonietta Mazzola","orcid":"0000-0003-2901-1742","position":4,"is_corresponding":false},{"id":244885,"name":"Sushrut Jangi","orcid":"0000-0001-5488-5770","position":5,"is_corresponding":false},{"id":1126904,"name":"Vanessa Beynon","orcid":"0000-0002-9719-1223","position":6,"is_corresponding":false},{"id":1127402,"name":"Junning Huang","orcid":null,"position":7,"is_corresponding":false},{"id":765894,"name":"Alessandro S. Farias","orcid":"0000-0001-6759-1819","position":8,"is_corresponding":false},{"id":700989,"name":"Anu Paul","orcid":"0000-0003-2479-8398","position":9,"is_corresponding":false},{"id":1126905,"name":"Leonilda Maria Barbosa dos Santos","orcid":"0000-0002-3600-9205","position":10,"is_corresponding":false},{"id":868360,"name":"Roopali Gandhi","orcid":null,"position":11,"is_corresponding":false},{"id":536738,"name":"Gopal Murugaiyan","orcid":"0000-0003-0439-1363","position":12,"is_corresponding":false},{"id":7840,"name":"Howard L. Weiner","orcid":"0000-0003-0203-9681","position":13,"is_corresponding":false},{"id":902682,"name":"Clare Baecher‐Allan","orcid":"0000-0003-2405-8525","position":14,"is_corresponding":false},{"id":1126902,"name":"Felipe von Glehn","orcid":"0000-0002-1004-7641","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T01:15:24.517012Z","pmid":"37175706","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":[]}