ArticleThe Journal of experimental medicine2023
Inherited human ITK deficiency impairs IFN-γ immunity and underlies tuberculosis.
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Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
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20citing papers in PubMed, 2 pooled it
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Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 24 citations in OpenAlex.
- Genetic, immunologic, and clinical features of 830 patients with Mendelian susceptibility to mycobacterial diseases (MSMD): A systematic review.The Journal of allergy and clinical immunology · 2024Pooled it
- Monogenic etiologies of persistent human papillomavirus infections: A comprehensive systematic review.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Pooled it
- Humans homozygous for rare or common hypomorphic IL23R variants are prone to tuberculosis.The Journal of experimental medicine · 2026Article
- Research on Gut Microbiota Features and Potential Biomarkers in Patients with Pulmonary Tuberculosis.Pathogens (Basel, Switzerland) · 2026Article
- Human inherited RORγT deficiency encompasses genetic heterogeneity, T cell deficiency, and clinical homogeneity.medRxiv : the preprint server for health sciences · 2026Article
- The host immune response to Mycobacterium tuberculosis determining protection or disease progression.Nature immunology · 2026Review
- Species-specific iNOS expression distinguishes epithelial and myeloid IFNγ responses in tuberculosis.bioRxiv : the preprint server for biology · 2026Article
- Translational potential of γδ T cells in hematologic diseases: from immunobiology to therapeutic innovation.Frontiers in immunology · 2026Review
- A Novel Compound Heterozygous Mutation in the IL12RB1 Gene Causes Susceptibility To Mycobacterium Tilburgii Infection.Journal of clinical immunology · 2025Article
- Human LY9 governs CD4Science immunology · 2025Article
- The monogenic landscape of human infectious diseases.The Journal of allergy and clinical immunology · 2025Review
- Peripheral blood cytokine expression levels and their clinical significance in children with influenza.Translational pediatrics · 2025Article
- Infectious adverse events associated with immune checkpoint inhibitors: a pharmacovigilance analysis based on FAERS database.Frontiers in immunology · 2025Article
- Impaired development of memory B cells and antibody responses in humans and mice deficient in PD-1 signaling.Immunity · 2024Article
- Article
- Epidermodysplasia Verruciformis and Vδ2 γδ T-cell Expansion in STK4 Deficiency.Journal of clinical immunology · 2024Article
- Human inherited PD-L1 deficiency is clinically and immunologically less severe than PD-1 deficiency.The Journal of experimental medicine · 2024Article
- γδ T cells: origin and fate, subsets, diseases and immunotherapy.Signal transduction and targeted therapy · 2023Review
- Interferons and Resistance Mechanisms in Tumors and Pathogen-Driven Diseases-Focus on the Major Histocompatibility Complex (MHC) Antigen Processing Pathway.International journal of molecular sciences · 2023Review
- Inborn errors of human transcription factors governing IFN-γ antimycobacterial immunity.Current opinion in immunology · 2023Review
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Authors and funding
44 authors at 14 institutions in 8 countries.
Masato OgishiSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY.ORCID 0000-0003-2421-7389
Rui Yang *St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY.ORCID 0000-0003-4427-2158
Rémy Rodriguez *Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, INSERM UMR1163, Paris, France.ORCID 0000-0003-3392-6371
Dominic P Golec *Cell Signaling and Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.ORCID 0000-0002-2741-3302
Emmanuel MartinLaboratory of Lymphocyte Activation and Susceptibility to EBV Infection, INSERM UMR1163, Paris, France.ORCID 0000-0003-4211-7373
Quentin PhilippotImagine Institute, University of Paris Cité, Paris, France.ORCID 0000-0003-3429-9605
Jonathan BohlenImagine Institute, University of Paris Cité, Paris, France.ORCID 0000-0003-0458-9484
Simon J PelhamSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY.ORCID 0000-0002-3119-662X
Andrés Augusto AriasSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY.ORCID 0000-0002-9478-8403
Taushif KhanDepartment of Immunology, Research Branch, Sidra Medicine, Doha, Qatar.ORCID 0000-0002-7917-8965
Manar AtaDepartment of Immunology, Research Branch, Sidra Medicine, Doha, Qatar.ORCID 0000-0001-7111-5719
Fatima Al AliDepartment of Immunology, Research Branch, Sidra Medicine, Doha, Qatar.ORCID 0000-0001-6451-7357
Flore RozenbergDepartment of Virology, Cochin Hospital, University of Paris, Paris, France.ORCID 0000-0001-7212-2021
Xiao-Fei KongSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY.ORCID 0000-0001-9983-2373
Maya ChrabiehImagine Institute, University of Paris Cité, Paris, France.ORCID 0000-0003-0772-4805
Candice LaineImagine Institute, University of Paris Cité, Paris, France.ORCID 0000-0003-3258-6969
Wei-Te LeiSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY.ORCID 0000-0003-1677-8901
Ji Eun HanSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY.ORCID 0000-0003-1112-9320
Yoann SeeleuthnerImagine Institute, University of Paris Cité, Paris, France.ORCID 0000-0002-1878-8567
Zenia KaulCell Signaling and Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.ORCID 0000-0002-3123-8164
Emmanuelle JouanguySt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY.ORCID 0000-0002-7358-9157
Vivien BéziatImagine Institute, University of Paris Cité, Paris, France.ORCID 0000-0002-4020-824X
Leila YoussefianDepartment of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Philadelphia, PA.ORCID 0000-0002-4253-6503
Hassan VahidnezhadDepartment of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Philadelphia, PA.ORCID 0000-0003-4298-9147
V Koneti RaoLaboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.ORCID 0000-0002-7881-6902
Bénédicte NevenPediatric Immunology and Hematology Department, Necker Hospital for Sick Children Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.ORCID 0000-0001-8941-0935
Claire FieschiClinical Immunology Department, Saint Louis Hospital, AP-HP Université de Paris, Paris, France.ORCID 0000-0003-2136-6178
Davood MansouriClinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.ORCID 0000-0002-0564-8282
Mohammad ShahrooeiDepartment of Microbiology and Immunology, Laboratory of Clinical Bacteriology and Mycology, KU Leuven, Leuven, Belgium.ORCID 0000-0002-4974-3441
Sevgi PekcanDepartment of Pediatric Pulmonology, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey.ORCID 0000-0002-8059-902X
Gulsum AlkanDivision of Pediatric Infectious Diseases, Department of Pediatrics, Selcuk University Faculty of Medicine, Konya, Turkey.ORCID 0000-0003-3384-769X
Melike EmiroğluDivision of Pediatric Infectious Diseases, Department of Pediatrics, Selcuk University Faculty of Medicine, Konya, Turkey.ORCID 0000-0003-1307-0246
Hüseyin TokgözDepartment of Pediatric Hematology, Meram School of Medicine, Necmettin Erbakan University, Konya, Turkey.ORCID 0000-0002-3064-4646
Jouni UittoDepartment of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Philadelphia, PA.ORCID 0000-0003-4639-807X
Fabian HauckLaboratory of Lymphocyte Activation and Susceptibility to EBV Infection, INSERM UMR1163, Paris, France.ORCID 0000-0001-9644-2003
Jacinta Bustamante *St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY.ORCID 0000-0002-3439-2482
Laurent Abel *St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY.ORCID 0000-0001-7016-6493
Sevgi Keles *Division of Pediatric Allergy and Immunology, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey.ORCID 0000-0001-7344-8947
Nima Parvaneh *Division of Allergy and Clinical Immunology, Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran.ORCID 0000-0002-3397-9716
Nico Marr *Department of Immunology, Research Branch, Sidra Medicine, Doha, Qatar.ORCID 0000-0002-1927-7072
Pamela L Schwartzberg *Cell Signaling and Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.ORCID 0000-0001-6318-9187
Sylvain Latour *Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, INSERM UMR1163, Paris, France.ORCID 0000-0001-8238-4391
Jean-Laurent Casanova *St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY.ORCID 0000-0002-7782-4169
Stéphanie Boisson-Dupuis *St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY.ORCID 0000-0002-7115-116X
Inserm · FRRockefeller University · USNational Institutes of Health · USNecmettin Erbakan University · TRThomas Jefferson University · USSelçuk University · TRAssistance Publique – Hôpitaux de Paris · FRHamad bin Khalifa University · QAHoward Hughes Medical Institute · USKU Leuven · BEMasih Daneshvari Hospital · IRTehran University of Medical Sciences · IRUniversidad de Antioquia · COUniversité Paris Cité · FR
Funding
Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational SuccessUL1TR001866 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY, KRUEGER, JAMES G · 2016 to 2025
$40.6MTissue and organ specific human B cell immunity: Supplement - Metabolic Risk Factors and Inflammation in PASC DevelopmentU19AI142737 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI TECTOR, A JOSEPH · 2019 to 2023
$19.7MGenetic and Biochemical Approaches to Tyrosine Kinase and Lymphocyte SignalingZIAAI001240 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SCHWARTZBERG, PAMELA · 2019 to 2025
$18.8MPharmacology & ImmunoPathology (PIP) CoreU19AI162568 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI EHRT, SABINE, GLICKMAN, MICHAEL S · 2021 to 2025
$13.0MClinical, Immunological and Genetic Analyses of ALPS and Related Immunedysregulatory DisordersZIAAI000732 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RAO, V KONETI · 2009 to 2025
$10.5MGenome-Wide Dissection of Mendelian Susceptibility to Mycobacterial DiseaseR01AI095983 · NIAID · ROCKEFELLER UNIVERSITY · PI BUSTAMANTE, JACINTA, CASANOVA, JEAN-LAURENT · 2021 to 2025
$2.5MA genetic and immunological investigation of JAK-STAT in the pathogenesis of Celiac DiseaseK08DK128631 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI KONG, XIAO-FEI · 2021 to 2025
$827kGenetic and immunological dissection of coinhibitory crosstalks between human T cells and cancer cellsF99CA274708 · NCI · ROCKEFELLER UNIVERSITY · PI OGISHI, MASATO · 2022 to 2023
$96kNCATS NIH HHS UL1 TR001866NCI NIH HHS F99 CA274708NIAID NIH HHS R01 AI095983NIAID NIH HHS U19 AI142737NIAID NIH HHS U19 AI162568NIDDK NIH HHS K08 DK128631
Abstract
Inborn errors of IFN-γ immunity can underlie tuberculosis (TB). We report three patients from two kindreds without EBV viremia or disease but with severe TB and inherited complete ITK deficiency, a condition associated with severe EBV disease that renders immunological studies challenging. They have CD4+ αβ T lymphocytopenia with a concomitant expansion of CD4-CD8- double-negative (DN) αβ and Vδ2- γδ T lymphocytes, both displaying a unique CD38+CD45RA+T-bet+EOMES- phenotype. Itk-deficient mice recapitulated an expansion of the γδ T and DN αβ T lymphocyte populations in the thymus and spleen, respectively. Moreover, the patients' T lymphocytes secrete small amounts of IFN-γ in response to TCR crosslinking, mitogens, or forced synapse formation with autologous B lymphocytes. Finally, the patients' total lymphocytes secrete small amounts of IFN-γ, and CD4+, CD8+, DN αβ T, Vδ2+ γδ T, and MAIT cells display impaired IFN-γ production in response to BCG. Inherited ITK deficiency undermines the development and function of various IFN-γ-producing T cell subsets, thereby underlying TB.
Indexed as
Receptors, Antigen, T-Cell, gamma-deltaTuberculosisAnimalsHumansInterferon-gammaMiceProtein-Tyrosine KinasesReceptors, Antigen, T-Cell, alpha-betaThymus GlandT-Lymphocyte Subsetsemt protein-tyrosine kinaseInterferon-gammaProtein-Tyrosine KinasesReceptors, Antigen, T-Cell, alpha-betaReceptors, Antigen, T-Cell, gamma-delta
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