{"doi":"10.1101/2020.08.31.274589","title":"Human T-bet governs innate and innate-like adaptive IFN-γ immunity against mycobacteria","abstract":"Summary Inborn errors of human IFN-γ immunity underlie mycobacterial disease. We report a patient with mycobacterial disease due to an inherited deficiency of the transcription factor T-bet. This deficiency abolishes the expression of T-bet target genes, including IFNG , by altering chromatin accessibility and DNA methylation in CD4 + T cells. The patient has profoundly diminished counts of mycobacterial-reactive circulating NK, invariant NKT (iNKT), mucosal-associated invariant T (MAIT), and Vδ2 + γδ T lymphocytes, and of non-mycobacterial-reactive classic T H 1 lymphocytes, the remainders of which also produce abnormally low amounts of IFN-γ. Other IFN-γ-producing lymphocyte subsets however develop normally, but with low levels of IFN-γ production, with exception of Vδ2 − γδ T lymphocytes, which produce normal amounts of IFN-γ in response to non-mycobacterial stimulation, and non-classic T H 1 (T H 1*) lymphocytes, which produce IFN-γ normally in response to mycobacterial antigens. Human T-bet deficiency thus underlies mycobacterial disease by preventing the development of, and IFN-γ production by, innate (NK) and innate-like adaptive lymphocytes (iNKT, MAIT, and Vδ2 + γδ T cells), with mycobacterial-specific, IFN-γ-producing, purely adaptive αβ T H 1* cells unable to compensate for this deficit.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":120747,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"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":218049,"name":"Federico Mele","orcid":"0000-0003-0455-4687","position":1,"is_corresponding":false},{"id":276383,"name":"Lisa Worley","orcid":null,"position":2,"is_corresponding":false},{"id":558864,"name":"David Langlais","orcid":"0000-0003-4429-0110","position":3,"is_corresponding":false},{"id":104146,"name":"Jérémie Rosain","orcid":"0000-0002-2822-161X","position":4,"is_corresponding":false},{"id":559809,"name":"Ibithal Benhsaien","orcid":null,"position":5,"is_corresponding":false},{"id":559810,"name":"Houda Elarabi","orcid":null,"position":6,"is_corresponding":false},{"id":478716,"name":"Carys A. 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