{"doi":"10.1038/s41598-021-84624-9","title":"IL-23p19 and CD5 antigen-like form a possible novel heterodimeric cytokine and contribute to experimental autoimmune encephalomyelitis development","abstract":"Abstract Among various cytokines, interleukin (IL)-12 family cytokines have very unique characteristics in that they are composed of two distinct subunits and these subunits are shared with each other. IL-23, one of the IL-12 family cytokines, consists of p19 and p40 subunits, is mainly produced by antigen-presenting cells, and plays a critical role in the expansion and maintenance of pathogenic helper CD4 + T (Th)17 cells. Since we initially found that p19 is secreted in the culture supernatant of activated CD4 + T cells, we have further investigated the role of p19. p19 was revealed to associate with CD5 antigen-like (CD5L), which is a repressor of Th17 pathogenicity and is highly expressed in non-pathogenic Th17 cells, to form a composite p19/CD5L. This p19/CD5L was shown to activate STAT5 and enhance the differentiation into granulocyte macrophage colony-stimulating factor (GM-CSF)-producing CD4 + T cells. Both CD4 + T cell-specific conditional p19-deficient mice and complete CD5L-deficient mice showed significantly alleviated experimental autoimmune encephalomyelitis (EAE) with reduced frequency of GM-CSF + CD4 + T cells. During the course of EAE, the serum level of p19/CD5L, but not CD5L, correlated highly with the clinical symptoms. Thus, the composite p19/CD5L is a possible novel heterodimeric cytokine that contributes to EAE development with GM-CSF up-regulation.","journal":"Scientific Reports","year":2021,"id":197331,"datarank":0.3958585994422889,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.0,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9643,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":448624,"name":"Izuru Mizoguchi","orcid":null,"position":1,"is_corresponding":false},{"id":448627,"name":"Naoko Orii","orcid":null,"position":2,"is_corresponding":false},{"id":447881,"name":"Shinya Inoué","orcid":"0000-0001-8639-6955","position":3,"is_corresponding":false},{"id":405454,"name":"Yasuhiro Katahira","orcid":"0000-0003-3493-1172","position":4,"is_corresponding":false},{"id":771915,"name":"Toshihiko Yoneto","orcid":null,"position":5,"is_corresponding":false},{"id":447882,"name":"Mingli Xu","orcid":"0000-0003-1079-461X","position":6,"is_corresponding":false},{"id":7866,"name":"Toru Miyazaki","orcid":"0000-0003-3842-4362","position":7,"is_corresponding":false},{"id":447888,"name":"Takayuki Yoshimoto","orcid":"0000-0002-2847-0341","position":8,"is_corresponding":false},{"id":448626,"name":"Hideaki Hasegawa","orcid":null,"position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:50:23.532351Z","pmid":"33664371","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":[]}