{"doi":"10.1084/jem.20182218","title":"USP22 controls iNKT immunity through MED1 suppression of histone H2A monoubiquitination","abstract":"The ubiquitin pathway has been shown to regulate iNKT cell immunity, but the deubiquitinase involved in this process has not been identified. Herein we found that ubiquitin-specific peptidase 22 (USP22) is highly expressed in iNKT cells during their early developmental stage 1. USP22 deficiency blocked the transition from stage 1 to 2 during iNKT cell development in a cell-intrinsic manner. USP22 suppression also diminishes iNKT17 and iNKT1 differentiation but favors iNKT2 polarization without altering conventional T cell activation and differentiation. USP22 interacts with the Mediator complex subunit 1 (MED1), a transcription coactivator involved in iNKT cell development. Interestingly, while interacting with MED1, USP22 does not function as a deubiquitinase to suppress MED1 ubiquitination for its stabilization. Instead, USP22 enhances MED1 functions for IL-2Rβ and T-bet gene expression through deubiquitinating histone H2A but not H2B monoubiquitination. Therefore, our study revealed USP22-mediated histone H2A deubiquitination fine-tunes MED1 transcriptional activation as a previously unappreciated molecular mechanism to control iNKT development and functions.","journal":"The Journal of Experimental Medicine","year":2020,"id":102130,"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":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9503,"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":499188,"name":"Yajun Wang","orcid":"0000-0002-7557-5883","position":1,"is_corresponding":false},{"id":499189,"name":"Beixue Gao","orcid":"0000-0002-4667-7995","position":2,"is_corresponding":false},{"id":500144,"name":"Yueqi Sun","orcid":null,"position":3,"is_corresponding":false},{"id":418080,"name":"Liang Cao","orcid":"0000-0001-5974-9815","position":4,"is_corresponding":false},{"id":418078,"name":"Samantha Genardi","orcid":"0000-0003-3133-5236","position":5,"is_corresponding":false},{"id":418084,"name":"Chyung‐Ru Wang","orcid":"0000-0002-9835-4784","position":6,"is_corresponding":false},{"id":499190,"name":"Hua‐Bin Li","orcid":"0000-0003-2332-8554","position":7,"is_corresponding":false},{"id":499191,"name":"Zhaolin Sun","orcid":"0000-0002-7684-6905","position":8,"is_corresponding":false},{"id":499192,"name":"Yanjie Yang","orcid":"0000-0002-8638-5313","position":9,"is_corresponding":false},{"id":240965,"name":"Deyu Fang","orcid":"0000-0002-4211-2751","position":10,"is_corresponding":false},{"id":240958,"name":"Yana Zhang","orcid":"0000-0003-4463-1827","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-18T22:40:51.552773Z","pmid":"32069354","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":[]}