{"doi":"10.1101/2020.05.06.080481","title":"Dectin-1 limits central nervous system autoimmunity through a non-canonical pathway","abstract":"ABSTRACT Pathologic roles for innate immunity in neurologic disorders are well-described, but protective aspects of the immune response are less understood. Dectin-1, a C-type lectin receptor (CLR), is largely known to induce inflammation. However, we found that Dectin-1 is protective in experimental autoimmune encephalomyelitis (EAE), while its canonical signaling mediator, Card9, promotes the disease. Notably, Dectin-1 does not respond to heat-killed Mycobacteria , an adjuvant to induce EAE. Myeloid cells mediate the protective function of Dectin-1 in EAE and upregulate gene expression of neuroprotective molecules, including Oncostatin M (Osm) through a non-canonical Card9-independent pathway, mediated by NFAT. Furthermore, we found that the Osm receptor (OsmR) functions specifically in astrocytes to reduce EAE severity. Our study revealed a new mechanism of protective myeloid-astrocyte crosstalk regulated by a non-canonical Dectin-1 pathway and identifies novel therapeutic targets for CNS autoimmunity. Graphical Abstract Dectin-1 is a protective C-type lectin receptor (CLR) in experimental autoimmune encephalomyelitis (EAE) Dectin-1 promotes expression of Osm , a neuroprotective IL-6 family cytokine, in myeloid cells OsmR signaling in astrocytes limits EAE progression and promotes remission Non-canonical Card9-independent signaling drives a distinct Dectin-1-mediated transcriptional program to induce expression of Osm and other factors with protective or anti-inflammatory functions","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":129501,"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":0.9549,"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":581812,"name":"Keiko Danzaki","orcid":null,"position":1,"is_corresponding":false},{"id":511472,"name":"Makoto Inoue","orcid":"0000-0002-3991-3806","position":2,"is_corresponding":false},{"id":581070,"name":"Emre Cardakli","orcid":"0000-0002-8473-0558","position":3,"is_corresponding":false},{"id":581813,"name":"Toshiaki Nonaka","orcid":null,"position":4,"is_corresponding":false},{"id":511470,"name":"Nupur Aggarwal","orcid":"0000-0002-7992-0023","position":5,"is_corresponding":false},{"id":511471,"name":"William E. Barclay","orcid":"0000-0002-6910-9157","position":6,"is_corresponding":false},{"id":233682,"name":"Ru‐Rong Ji","orcid":"0000-0002-9355-3688","position":7,"is_corresponding":false},{"id":249988,"name":"Mari L. Shinohara","orcid":"0000-0002-6808-9844","position":8,"is_corresponding":false},{"id":308941,"name":"M. Elizabeth Deerhake","orcid":"0000-0003-4061-5766","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-18T23:15:49.682497Z","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":[]}