{"doi":"10.1172/jci122732","title":"EBV-induced gene 3 augments IL-23Rα protein expression through a chaperone calnexin","abstract":"Epstein-Barr virus-induced gene 3 (EBI3) is a subunit common to IL-27, IL-35, and IL-39. Here, we explore an intracellular role of EBI3 that is independent of its function in cytokines. EBI3-deficient naive CD4+ T cells had reduced IFN-γ production and failed to induce T cell-dependent colitis in mice. Similarly reduced IFN-γ production was observed in vitro in EBI3-deficient CD4+ T cells differentiated under pathogenic Th17 polarizing conditions with IL-23. This is because the induction of expression of one of the IL-23 receptor (IL-23R) subunits, IL-23Rα, but not another IL-23R subunit, IL-12Rβ1, was selectively decreased at the protein level, but not the mRNA level. EBI3 augmented IL-23Rα expression via binding to the chaperone molecule calnexin and to IL-23Rα in a peptide-dependent manner, but not a glycan-dependent manner. Indeed, EBI3 failed to augment IL-23Rα expression in the absence of endogenous calnexin. Moreover, EBI3 poorly augmented the expression of G149R, an IL-23Rα variant that protects against the development of human colitis, because binding of EBI3 to the variant was reduced. Taken together with the result that EBI3 expression is inducible in T cells, the present results suggest that EBI3 plays a critical role in augmenting IL-23Rα protein expression via calnexin under inflammatory conditions.","journal":"Journal of Clinical Investigation","year":2020,"id":88408,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"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":448625,"name":"Mio Ohashi","orcid":null,"position":1,"is_corresponding":false},{"id":448626,"name":"Hideaki Hasegawa","orcid":null,"position":2,"is_corresponding":false},{"id":447880,"name":"Yukino Chiba","orcid":"0000-0003-0448-0737","position":3,"is_corresponding":false},{"id":448627,"name":"Naoko Orii","orcid":null,"position":4,"is_corresponding":false},{"id":447881,"name":"Shinya Inoué","orcid":"0000-0001-8639-6955","position":5,"is_corresponding":false},{"id":448628,"name":"Chiaki Kawana","orcid":null,"position":6,"is_corresponding":false},{"id":447882,"name":"Mingli Xu","orcid":"0000-0003-1079-461X","position":7,"is_corresponding":false},{"id":447883,"name":"Katsuko Sudo","orcid":"0000-0002-5286-7648","position":8,"is_corresponding":false},{"id":447884,"name":"Koji Fujita","orcid":"0000-0001-9390-7565","position":9,"is_corresponding":false},{"id":447885,"name":"Masahiko Kuroda","orcid":"0000-0001-7052-4289","position":10,"is_corresponding":false},{"id":447886,"name":"Shinichi Hashimoto","orcid":"0000-0002-1223-2349","position":11,"is_corresponding":false},{"id":447887,"name":"Kouji Matsushima","orcid":"0000-0003-1056-171X","position":12,"is_corresponding":false},{"id":447888,"name":"Takayuki Yoshimoto","orcid":"0000-0002-2847-0341","position":13,"is_corresponding":false},{"id":448624,"name":"Izuru Mizoguchi","orcid":null,"position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:00:56.736935Z","pmid":"32809973","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":[]}