{"doi":"10.1084/jem.20211273","title":"A partial form of inherited human USP18 deficiency underlies infection and inflammation","abstract":"Human USP18 is an interferon (IFN)-stimulated gene product and a negative regulator of type I IFN (IFN-I) signaling. It also removes covalently linked ISG15 from proteins, in a process called deISGylation. In turn, ISG15 prevents USP18 from being degraded by the proteasome. Autosomal recessive complete USP18 deficiency is life-threatening in infancy owing to uncontrolled IFN-I-mediated autoinflammation. We report three Moroccan siblings with autoinflammation and mycobacterial disease who are homozygous for a new USP18 variant. We demonstrate that the mutant USP18 (p.I60N) is normally stabilized by ISG15 and efficient for deISGylation but interacts poorly with the receptor-anchoring STAT2 and is impaired in negative regulation of IFN-I signaling. We also show that IFN-γ-dependent induction of IL-12 and IL-23 is reduced owing to IFN-I-mediated impairment of myeloid cells to produce both cytokines. Thus, insufficient negative regulation of IFN-I signaling by USP18-I60N underlies a specific type I interferonopathy, which impairs IL-12 and IL-23 production by myeloid cells, thereby explaining predisposition to mycobacterial disease.","journal":"The Journal of Experimental Medicine","year":2022,"id":235730,"datarank":0.6515708132780527,"base_score":4.343805421853684,"endowment":4.343805421853684,"self_citation_contribution":0.6515708132780527,"citation_network_contribution":0.0,"self_endowment_contribution":0.6515708132780527,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":76,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9441,"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":265879,"name":"Sofija Buta","orcid":"0000-0001-7662-3851","position":1,"is_corresponding":false},{"id":618891,"name":"Tom Le Voyer","orcid":"0000-0002-7253-3135","position":2,"is_corresponding":false},{"id":273554,"name":"Zhi Li","orcid":"0000-0003-4422-4914","position":3,"is_corresponding":false},{"id":854633,"name":"Lasse Toftdal Dynesen","orcid":"0000-0003-3881-7131","position":4,"is_corresponding":false},{"id":854634,"name":"Françoise Vuillier","orcid":"0000-0002-5551-9876","position":5,"is_corresponding":false},{"id":854635,"name":"Lina Franklin","orcid":"0000-0002-0433-7183","position":6,"is_corresponding":false},{"id":270308,"name":"Fatima Ailal","orcid":"0000-0001-5824-3193","position":7,"is_corresponding":false},{"id":742513,"name":"Alice Muglia Thomaz da Silva Amancio","orcid":"0000-0003-1098-8799","position":8,"is_corresponding":false},{"id":105220,"name":"Louise Malle","orcid":"0000-0001-9704-9756","position":9,"is_corresponding":false},{"id":105215,"name":"Conor Gruber","orcid":"0000-0002-9102-8134","position":10,"is_corresponding":false},{"id":672535,"name":"Ibtihal Benhsaien","orcid":"0000-0001-5727-9629","position":11,"is_corresponding":false},{"id":270310,"name":"Jennie Altman","orcid":"0000-0003-3239-1643","position":12,"is_corresponding":false},{"id":270309,"name":"Justin Taft","orcid":"0000-0002-9998-0429","position":13,"is_corresponding":false},{"id":263166,"name":"Caroline Deswarte","orcid":"0000-0002-8775-3368","position":14,"is_corresponding":false},{"id":263169,"name":"Manon Roynard","orcid":"0000-0003-0668-002X","position":15,"is_corresponding":false},{"id":657341,"name":"Alejandro Nieto-Patlán","orcid":"0000-0002-8668-6853","position":16,"is_corresponding":false},{"id":670958,"name":"Kunihiko Moriya","orcid":"0000-0002-0418-5132","position":17,"is_corresponding":false},{"id":104146,"name":"Jérémie Rosain","orcid":"0000-0002-2822-161X","position":18,"is_corresponding":false},{"id":285471,"name":"Nathalie Boddaert","orcid":"0000-0003-0991-7774","position":19,"is_corresponding":false},{"id":243781,"name":"Aziz Bousfiha","orcid":null,"position":20,"is_corresponding":false},{"id":274413,"name":"Yanick J. Crow","orcid":"0000-0001-7211-7564","position":21,"is_corresponding":false},{"id":313436,"name":"Dragana Janković","orcid":"0000-0001-7360-1809","position":22,"is_corresponding":false},{"id":330710,"name":"Alan Sher","orcid":"0000-0001-7053-2895","position":23,"is_corresponding":false},{"id":57373,"name":"Jean-Laurent Casanova","orcid":"0000-0002-7782-4169","position":24,"is_corresponding":false},{"id":273555,"name":"Sandra Pellegrini","orcid":"0000-0001-5837-7589","position":25,"is_corresponding":false},{"id":241304,"name":"Jacinta Bustamante","orcid":"0000-0002-3439-2482","position":26,"is_corresponding":false},{"id":105284,"name":"Dusan Bogunovic","orcid":"0000-0002-9277-3232","position":27,"is_corresponding":false},{"id":270307,"name":"Marta Martín-Fernández","orcid":"0000-0003-4671-6349","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:21:53.333008Z","pmid":"35258551","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":[]}