{"doi":"10.1126/sciimmunol.aba0570","title":"Oral epithelial IL-22/STAT3 signaling licenses IL-17–mediated immunity to oral mucosal candidiasis","abstract":"Interleukin-17 (IL-17) and IL-22 are cytokines produced by type 17 lymphocytes. Both cytokines mediate antifungal immunity yet activate quite distinct downstream signaling pathways. While much is now understood about how IL-17 promotes immunity in OPC, the activities of IL-22 are far less well delineated. We show that, despite having similar requirements for induction from type 17 cells, IL-22 and IL-17 function nonredundantly during OPC. We find that the IL-22 and IL-17 receptors are required in anatomically distinct locations within the oral mucosa; loss of IL-22RA1 or signal transducer and activator of transcription 3 (STAT3) in the oral basal epithelial layer (BEL) causes susceptibility to OPC, whereas IL-17RA is needed in the suprabasal epithelial layer (SEL). Transcriptional profiling of the tongue linked IL-22/STAT3 not only to oral epithelial cell proliferation and survival but also, unexpectedly, to driving an IL-17-specific gene signature. We show that IL-22 mediates regenerative signals on the BEL that replenish the IL-17RA-expressing SEL, thereby restoring the ability of the oral epithelium to respond to IL-17 and thus to mediate antifungal events. Consequently, IL-22 signaling in BEL \"licenses\" IL-17 signaling in the oral mucosa, revealing spatially distinct yet cooperative activities of IL-22 and IL-17 in oral candidiasis.","journal":"Science Immunology","year":2020,"id":53435,"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":117,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9412,"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":272362,"name":"Timothy J. Break","orcid":"0000-0001-5987-7817","position":1,"is_corresponding":false},{"id":272363,"name":"Giraldina Trevejo-Nuñez","orcid":"0000-0002-9770-763X","position":2,"is_corresponding":false},{"id":272364,"name":"Natasha Whibley","orcid":"0000-0001-5765-1646","position":3,"is_corresponding":false},{"id":272365,"name":"Bianca M. Coleman","orcid":"0000-0003-4276-7456","position":4,"is_corresponding":false},{"id":272366,"name":"Rachel D. Bailey","orcid":"0000-0002-2046-2339","position":5,"is_corresponding":false},{"id":271263,"name":"Daniel H. Kaplan","orcid":"0000-0003-0598-0047","position":6,"is_corresponding":false},{"id":272367,"name":"Julian R. Naglik","orcid":"0000-0002-8072-7917","position":7,"is_corresponding":false},{"id":272368,"name":"Wei Shan","orcid":"0000-0003-0344-5729","position":8,"is_corresponding":false},{"id":242912,"name":"Amol C. Shetty","orcid":"0000-0001-8790-7649","position":9,"is_corresponding":false},{"id":59073,"name":"Carrie McCracken","orcid":"0000-0002-8038-9727","position":10,"is_corresponding":false},{"id":272369,"name":"Scott K. Durum","orcid":"0000-0003-1307-9582","position":11,"is_corresponding":false},{"id":272370,"name":"Partha S. Biswas","orcid":"0000-0002-4570-7443","position":12,"is_corresponding":false},{"id":272371,"name":"Vincent M. Bruno","orcid":"0000-0003-1683-2015","position":13,"is_corresponding":false},{"id":246970,"name":"Jay K. Kolls","orcid":"0000-0001-5151-6304","position":14,"is_corresponding":false},{"id":104225,"name":"Michail S. Lionakis","orcid":"0000-0003-4994-9500","position":15,"is_corresponding":false},{"id":37710,"name":"Sarah L. Gaffen","orcid":"0000-0001-8511-2041","position":16,"is_corresponding":false},{"id":272361,"name":"Felix E.Y. Aggor","orcid":"0000-0002-0327-0095","position":0,"is_corresponding":true}],"reference_count":112,"raw_metadata":null,"created_at":"2026-07-18T20:44:25.349797Z","pmid":"32503875","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":[]}