ArticleThe Journal of experimental medicine2022
Impaired IL-23-dependent induction of IFN-γ underlies mycobacterial disease in patients with inherited TYK2 deficiency.
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Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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43citing papers in PubMed, 1 pooled it
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 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
- Humans homozygous for rare or common hypomorphic IL23R variants are prone to tuberculosis.The Journal of experimental medicine · 2026Article
- Human inherited RORγT deficiency encompasses genetic heterogeneity, T cell deficiency, and clinical homogeneity.medRxiv : the preprint server for health sciences · 2026Article
- Deep mutational scanning reveals pharmacologically relevant insights into TYK2 signaling and disease.eLife · 2026Article
- How Genomic and Structural Context Could Shape JAK-STAT Variant Pathogenicity.Twin research and human genetics : the official journal of the International Society for Twin Studies · 2026Article
- Monogenic disorders of immunity: Common variants are not so rare.Cell genomics · 2026Review
- Mendelian susceptibility to mycobacterial disease: IFN-γ-driven immunity collapse underlies heterogeneous infections.Frontiers in immunology · 2026Review
- T cell-macrophage interactions in tuberculosis: What we've got here is failure to communicate.Journal of internal medicine · 2026Review
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- Atopic dermatitis in inborn errors of immunity: at the interface of immunodeficiency and immune dysregulation.Immunologic research · 2025Review
- Mepolizumab treatment in a child with inherited TYK2 deficiency.Journal of human immunity · 2025Article
- Pathological IgE Production in Inborn Errors of Immunity and Beyond.Immunological reviews · 2025Review
- Human LY9 governs CD4Science immunology · 2025Article
- The monogenic landscape of human infectious diseases.The Journal of allergy and clinical immunology · 2025Review
- Advances in understanding the role of interleukins in pulmonary fibrosis (Review).Experimental and therapeutic medicine · 2025Review
- JAK/STAT in human diseases: a common axis in immunodeficiencies and hematological disorders.Frontiers in immunology · 2025Review
- Lack of TYK2 signaling enhances host resistance to Candida albicans skin infection.Nature communications · 2024Article
- Review
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Authors and funding
67 authors at 20 institutions in 15 countries.
Masato Ogishi *St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0003-2421-7389
Andrés Augusto Arias *St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0002-9478-8403
Rui Yang *St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0003-4427-2158
Ji Eun Han *St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0003-1112-9320
Peng ZhangSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0002-6129-567X
Darawan RinchaiSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0001-8851-7730
Joshua HalpernSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0003-0272-5497
Jeanette MulwaSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0003-0900-1280
Narelle KeatingSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0002-4392-0806
Maya ChrabiehLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.ORCID 0000-0003-0772-4805
Candice LainéLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.ORCID 0000-0003-3258-6969
Yoann SeeleuthnerLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.ORCID 0000-0002-1878-8567
Noé Ramírez-AlejoSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0001-7079-1811
Nioosha Nekooie-MarnanyAcquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.ORCID 0000-0002-0479-582X
Andrea GuennounSidra Medicine, Doha, Qatar.ORCID 0000-0002-4303-8653
Ingrid Muller-FleckensteinInstitute of Clinical and Molecular Virology, University of Erlangen-Nuremberg, Erlangen, Germany.
Bernhard FleckensteinInstitute of Clinical and Molecular Virology, University of Erlangen-Nuremberg, Erlangen, Germany.ORCID 0000-0002-4687-469X
Sara S KilicDepartment of Pediatric Immunology and Rheumatology, Faculty of Medicine, Uludag University, Bursa, Turkey.ORCID 0000-0001-8571-2581
Yoshiyuki MinegishiDivision of Molecular Medicine, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.ORCID 0000-0002-9613-8586
Stephan EhlInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID 0000-0002-9265-2721
Petra Kaiser-LabuschEltern- Kind -Zentrum Prof. Hess, Klinikum Bremen-Mitte, Bremen, Germany.ORCID 0000-0002-3229-6083
Yasemin Kendir-DemirkolDepartment of Pediatric Genetics, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey.ORCID 0000-0001-8016-5224
Flore RozenbergLaboratory of Virology, Assistance Publique-Hôpitaux de Paris, Cochin Hospital, Paris, France.ORCID 0000-0001-7212-2021
Abderrahmane ErramiLaboratory of Clinical Immunology, Inflammation and Allergy, Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.ORCID 0000-0002-2916-5007
Shen-Ying ZhangSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0002-9449-3672
Qian ZhangSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0002-9040-3289
Jonathan BohlenLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.ORCID 0000-0003-0458-9484
Quentin PhilippotLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.ORCID 0000-0003-3429-9605
Anne PuelSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0003-2603-0323
Emmanuelle JouanguySt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0002-7358-9157
Zahra Pourmoghaddas *Department of Pediatric Infectious Disease, Isfahan University of Medical Sciences, Isfahan, Iran.ORCID 0000-0002-5424-3919
Shahrzad Bakhtiar *Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Department for Child and Adolescent Medicine, University Hospital Frankfurt, Frankfurt, Germany.ORCID 0000-0002-9898-1542
Andre M Willasch *Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Department for Child and Adolescent Medicine, University Hospital Frankfurt, Frankfurt, Germany.ORCID 0000-0001-6798-8998
Gerd Horneff *Center for Pediatric Rheumatology, Department of Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin, Germany.ORCID 0000-0001-5491-7832
Genevieve Llanora *Division of Allergy and Immunology, Department of Paediatrics, Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore.ORCID 0000-0001-9282-8435
Lynette P Shek *Division of Allergy and Immunology, Department of Paediatrics, Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore.ORCID 0000-0001-9064-8983
Louis Y A Chai *Division of Infectious Diseases, Department of Medicine, National University Health System, Singapore.ORCID 0000-0002-9640-0791
Sen Hee Tay *Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.ORCID 0000-0002-7907-5288
Hamid H Rahimi *Department of Pediatrics, Isfahan University of Medical Sciences, Isfahan, Iran.ORCID 0000-0002-4925-5253
Seyed Alireza Mahdaviani *Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.ORCID 0000-0001-6224-4797
Serdar Nepesov *Department of Pediatric Allergy and Immunology, Istanbul Medipol University, Istanbul, Turkey.ORCID 0000-0002-4551-5433
Aziz A Bousfiha *Clinical Immunology Unit, Department of Pediatrics, King Hassan II University, Ibn-Rochd Hospital, Casablanca, Morocco.ORCID 0000-0002-5011-9873
Emine Hafize Erdeniz *Division of Pediatric Infectious Diseases, Ondokuz Mayıs University, Samsun, Turkey.ORCID 0000-0003-2669-0890
Adem Karbuz *Division of Pediatric Infectious Diseases, Okmeydani Training and Research Hospital, University of Health Sciences, Istanbul, Turkey.ORCID 0000-0002-5460-3638
Nico Marr *Sidra Medicine, Doha, Qatar.ORCID 0000-0002-1927-7072
Carmen Navarrete *Department of Immunology, Hospital de Niños Roberto del Río, Santiago de Chile, Chile.ORCID 0000-0002-8867-1858
Mehdi Adeli *Division of Allergy and Immunology, Sidra Medicine/Hamad Medical Corp., Doha, Qatar.ORCID 0000-0002-3051-3080
Lennart Hammarstrom *Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden.ORCID 0000-0002-8635-9609
Hassan Abolhassani *Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden.ORCID 0000-0002-4838-0407
Nima Parvaneh *Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.ORCID 0000-0002-3397-9716
Saleh Al Muhsen *Immunology Research Laboratory, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.ORCID 0000-0003-3698-9968
Mohammed F Alosaimi *Immunology Research Laboratory, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.ORCID 0000-0002-8025-3491
Fahad Alsohime *Pediatric Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia.ORCID 0000-0002-4979-3895
Maryam Nourizadeh *Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Mostafa Moin *Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Rand Arnaout *Section of Allergy & Immunology, Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.ORCID 0000-0003-3951-5880
Saad Alshareef *Section of Allergy & Immunology, Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.ORCID 0000-0001-9787-6380
Jamila El-Baghdadi *Genetics Unit, Mohamed V Military Hospital, Hay Riad, Rabat, Morocco.ORCID 0000-0002-1920-2310
Ferah Genel *University of Health Sciences, Dr Behçet Uz Children's Hospital, Division of Pediatric Immunology, Izmir, Turkey.ORCID 0000-0002-9976-067X
Roya Sherkat *Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.ORCID 0000-0002-8574-2091
Ayça Kiykim *Pediatric Allergy and Immunology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey.ORCID 0000-0001-5821-3963
Esra Yücel *Division of Pediatric Allergy and Immunology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.ORCID 0000-0003-3712-2522
Sevgi Keles *Division of Pediatric Allergy and Immunology, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey.ORCID 0000-0001-7344-8947
Jacinta Bustamante *St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0002-3439-2482
Laurent Abel *St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0001-7016-6493
Jean-Laurent Casanova *St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0002-7782-4169
Stéphanie Boisson-Dupuis *St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0002-7115-116X
Inserm · FRRockefeller University · USIsfahan University of Medical Sciences · IRChildren's Medical Center · IRNational University of Singapore · SGFriedrich-Alexander-Universität Erlangen-Nürnberg · DEGoethe University Frankfurt · DEKing Saud University · SASağlık Bilimleri Üniversitesi · TRUniversity of Hassan II Casablanca · MAAlfaisal University · SABGI Group (China) · CNBursa Uludağ Üni̇versi̇tesi̇ · TRHamad Medical Corporation · QAHôpital Cochin · FRHôpital Militaire Moulay Ismail · MAHospital Roberto del Rio · CLHoward Hughes Medical Institute · USIstanbul Medipol University · TRIstanbul University · TR
Funding
Viable but Nonculturable MtbU19AI111143 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI FITZGERALD, DANIEL W, GLICKMAN, MICHAEL S · 2014 to 2020
$48.6MDeveloping, 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
$19.7MPharmacology & ImmunoPathology (PIP) CoreU19AI162568 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI EHRT, SABINE, GLICKMAN, MICHAEL S · 2021 to 2025
$13.0MInborn errors of immunity in patients with life-threatening COVID-19R01AI163029 · NIAID · ROCKEFELLER UNIVERSITY · PI CASANOVA, JEAN-LAURENT, ZHANG, QIAN · 2021 to 2025
$3.7MGenome-Wide Dissection of Mendelian Susceptibility to Mycobacterial DiseaseR01AI095983 · NIAID · ROCKEFELLER UNIVERSITY · PI BUSTAMANTE, JACINTA, CASANOVA, JEAN-LAURENT · 2021 to 2025
$2.5MGenetic and immunological dissection of coinhibitory crosstalks between human T cells and cancer cellsF99CA274708 · NCI · ROCKEFELLER UNIVERSITY · PI OGISHI, MASATO · 2022 to 2023
$96kHoward Hughes Medical InstituteNCATS NIH HHS UL1 TR001866NCI NIH HHS F99 CA274708NIAID NIH HHS R01 AI095983NIAID NIH HHS R01 AI163029NIAID NIH HHS U19 AI111143NIAID NIH HHS U19 AI142737NIAID NIH HHS U19 AI162568
Abstract
Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/β (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23-dependent induction of IFN-γ is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling.
Indexed as
Job SyndromeTYK2 KinaseHumansInterferon-gammaInterleukin-23Interferon-gammaInterleukin-23TYK2 KinaseTYK2 protein, human
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