{"doi":"10.1101/2022.01.03.474823","title":"Cell type specific IL-27p28 (IL-30) deletion uncovers an unexpected regulatory function of IL-30 in autoimmune inflammation","abstract":"Abstract IL-27 is an IL-12 family cytokine with immune regulatory properties, capable of modulating inflammatory responses, including autoimmunity. While extensive studies investigated the major target cells of IL-27 mediating its functions, the source of IL-27 especially during tissue specific autoimmune inflammation has not formally been examined. IL-27p28 subunit, also known as IL-30, was initially discovered as an IL-27-specific subunit, and it has thus been deemed as a surrogate marker to denote IL-27 expression. However, IL-30 can be secreted independently of Ebi3, a subunit that forms bioactive IL-27 with IL-30. Moreover, IL-30 itself may act as a negative regulator antagonizing IL-27. In this study, we exploited various cell type specific IL-30-deficient mouse models and examined the source of IL-30 in T cell mediated autoimmune neuroinflammation. We found that IL-30 expressed by infiltrating and CNS resident APC subsets, infiltrating myeloid cells, microglia, and astrocytes, is key limiting the inflammation. However, dendritic cell-derived IL-30 was dispensable for the disease development. Unexpectedly, in cell type specific IL-30 deficient mice that develop severe EAE, IL-30 expression in the remaining wild-type APC subsets is disproportionately increased, suggesting that increased endogenous IL-30 production may be involved in the severe pathogenesis. In support, systemic recombinant IL-30 administration induced severe EAE. Our results demonstrate that dysregulated endogenous IL-30 expression may interfere with immune regulatory functions of IL-27, promoting encephalitogenic inflammation in vivo.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":305338,"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":0.9581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":278884,"name":"Sohee Kim","orcid":"0000-0003-0451-0959","position":1,"is_corresponding":false},{"id":999624,"name":"Myung-su Kang","orcid":null,"position":2,"is_corresponding":false},{"id":567349,"name":"Zhinan Yin","orcid":"0000-0001-6524-8777","position":3,"is_corresponding":false},{"id":278889,"name":"Booki Min","orcid":"0000-0002-2151-9413","position":4,"is_corresponding":false},{"id":278881,"name":"Dongkyun Kim","orcid":"0000-0002-0156-4719","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T00:32:41.290883Z","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":[]}