Human T-bet Governs Innate and Innate-like Adaptive IFN-γ Immunity against Mycobacteria

Inborn errors of human interferon gamma (IFN-γ) immunity underlie mycobacterial disease. We report a patient with mycobacterial disease due to inherited deficiency of the transcription factor T-bet. The patient has extremely low counts of circulating Mycobacterium-reactive natural killer (NK), invar...

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Bibliographic Details
Published in:	Cell Vol. 183; no. 7; p. 1826
Main Authors:	Yang, Rui, Mele, Federico, Worley, Lisa, Langlais, David, Rosain, Jérémie, Benhsaien, Ibithal, Elarabi, Houda, Croft, Carys A, Doisne, Jean-Marc, Zhang, Peng, Weisshaar, Marc, Jarrossay, David, Latorre, Daniela, Shen, Yichao, Han, Jing, Ogishi, Masato, Gruber, Conor, Markle, Janet, Al Ali, Fatima, Rahman, Mahbuba, Khan, Taushif, Seeleuthner, Yoann, Kerner, Gaspard, Husquin, Lucas T, Maclsaac, Julia L, Jeljeli, Mohamed, Errami, Abderrahmane, Ailal, Fatima, Kobor, Michael S, Oleaga-Quintas, Carmen, Roynard, Manon, Bourgey, Mathieu, El Baghdadi, Jamila, Boisson-Dupuis, Stéphanie, Puel, Anne, Batteux, Fréderic, Rozenberg, Flore, Marr, Nico, Pan-Hammarström, Qiang, Bogunovic, Dusan, Quintana-Murci, Lluis, Carroll, Thomas, Ma, Cindy S, Abel, Laurent, Bousfiha, Aziz, Di Santo, James P, Glimcher, Laurie H, Gros, Philippe, Tangye, Stuart G, Sallusto, Federica, Bustamante, Jacinta, Casanova, Jean-Laurent
Format:	Journal Article
Language:	English
Published:	United States 23.12.2020
Subjects:	Adaptive Immunity Amino Acid Sequence Base Sequence Cell Lineage Child, Preschool Chromatin - metabolism CpG Islands - genetics Dendritic Cells - metabolism DNA Methylation - genetics Epigenesis, Genetic Female Homozygote Humans Immunity, Innate INDEL Mutation - genetics Infant Interferon-gamma - immunology Interferon-gamma - metabolism Killer Cells, Natural - cytology Killer Cells, Natural - metabolism Loss of Function Mutation - genetics Male Mycobacterium - immunology Mycobacterium Infections - genetics Mycobacterium Infections - immunology Mycobacterium Infections - microbiology Pedigree T-bet Transcription Factor T-Box Domain Proteins - chemistry T-Box Domain Proteins - deficiency T-Box Domain Proteins - genetics T-Box Domain Proteins - metabolism T-Lymphocytes, Helper-Inducer - immunology Transcriptome - genetics innate-like adaptive lymphocyte IFN-γ innate lymphocyte mycobacterium immunodeficiency inborn errors of immunity Mendelian susceptibility to mycobacterial disease T-bet
ISSN:	1097-4172, 1097-4172
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Summary:	Inborn errors of human interferon gamma (IFN-γ) immunity underlie mycobacterial disease. We report a patient with mycobacterial disease due to inherited deficiency of the transcription factor T-bet. The patient has extremely low counts of circulating Mycobacterium-reactive natural killer (NK), invariant NKT (iNKT), mucosal-associated invariant T (MAIT), and Vδ2 γδ T lymphocytes, and of Mycobacterium-non reactive classic T 1 lymphocytes, with the residual populations of these cells also producing abnormally small amounts of IFN-γ. Other lymphocyte subsets develop normally but produce low levels of IFN-γ, with the exception of CD8 αβ T and non-classic CD4 αβ T 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 innate (NK) and innate-like adaptive lymphocytes (iNKT, MAIT, and Vδ2 γδ T cells) and IFN-γ production by them, with mycobacterium-specific, IFN-γ-producing, purely adaptive CD8 αβ T, and CD4 αβ T 1 cells unable to compensate for this deficit.
Bibliography:	ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3
ISSN:	1097-4172 1097-4172
DOI:	10.1016/j.cell.2020.10.046