Impaired IL-23-dependent induction of IFN-gamma underlies mycobacterial disease in patients with inherited TYK2 deficiency

Masato Ogishi; Andres Augusto Arias; Rui Yang; Ji Eun Han; Peng Zhang; Darawan Rinchai; Joshua Halpern; Jeanette Mulwa; Narelle Keating; Maya Chrabieh; Candice Laine; Yoann Seeleuthner; Noe Ramirez-Alejo; Nioosha Nekooie-Marnany; Andrea Guennoun; Ingrid Muller-Fleckenstein; Bernhard Fleckenstein; Sara S. Kilic; Yoshiyuki Minegishi; Stephan Ehl; Petra Kaiser-Labusch; Yasemin Kendir-Demirkol; Flore Rozenberg; Abderrahmane Errami; Shen-Ying Zhang; Qian Zhang; Jonathan Bohlen; Anne Puel; Emmanuelle Jouanguy; Zahra Pourmoghaddas; Shahrzad Bakhtiar; Andre M. Willasch; Gerd Horneff; Genevieve Llanora; Lynette P. Shek; Louis Y. A. Chai; Sen Hee Tay; Hamid H. Rahimi; Seyed Alireza Mahdaviani; Serdar Nepesov; Aziz A. Bousfiha; Emine Hafize Erdeniz; Adem Karbuz; Nico Marr; Carmen Navarrete; Mehdi Adeli; Lennart Hammarstrom; Hassan Abolhassani; Nima Parvaneh; Saleh Al Muhsen; Mohammed F. Alosaimi; Fahad Alsohime; Maryam Nourizadeh; Mostafa Moin; Rand Arnaout; Saad Alshareef; Jamila El-Baghdadi; Ferah Genel; Roya Sherkat; Ayca Kiykim; Esra Yucel; Sevgi Keles; Jacinta Bustamante; Laurent Abel; Jean-Laurent Casanova; Stephanie Boisson-Dupuis

doi:10.1084/jem.20220094

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Impaired IL-23-dependent induction of IFN-gamma underlies mycobacterial disease in patients with inherited TYK2 deficiency

Journal article

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Peer reviewed

Impaired IL-23-dependent induction of IFN-gamma underlies mycobacterial disease in patients with inherited TYK2 deficiency

Masato Ogishi, Andres Augusto Arias, Rui Yang, Ji Eun Han, Peng Zhang, Darawan Rinchai, Joshua Halpern, Jeanette Mulwa, Narelle Keating, Maya Chrabieh, …

The Journal of experimental medicine, Vol.219(10)

03/10/2022

DOI: https://doi.org/10.1084/jem.20220094

PMID: 36094518

Abstract

Immunology

Life Sciences & Biomedicine

Medicine, Research & Experimental

Research & Experimental Medicine

Science & Technology

Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-alpha/beta (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-gamma 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.

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Title: Impaired IL-23-dependent induction of IFN-gamma underlies mycobacterial disease in patients with inherited TYK2 deficiency
Creators - without role: Masato Ogishi - Rockefeller University
Andres Augusto Arias - Rockefeller University
Rui Yang - Rockefeller University
Ji Eun Han - Rockefeller University
Peng Zhang - Rockefeller University
Darawan Rinchai - Rockefeller University
Joshua Halpern - Rockefeller University
Jeanette Mulwa - Rockefeller University
Narelle Keating - Rockefeller University
Maya Chrabieh - Inserm
Candice Laine - Inserm
Yoann Seeleuthner - Inserm
Noe Ramirez-Alejo - Rockefeller University
Nioosha Nekooie-Marnany - Isfahan University of Medical Sciences
Andrea Guennoun - Qatar Airways
Ingrid Muller-Fleckenstein - Friedrich-Alexander-Universität Erlangen-Nürnberg
Bernhard Fleckenstein - Friedrich-Alexander-Universität Erlangen-Nürnberg
Sara S. Kilic - Uludağ University
Yoshiyuki Minegishi - Tokushima University
Stephan Ehl - University of Freiburg
Petra Kaiser-Labusch - Klinikum Bremen-Mitte
Yasemin Kendir-Demirkol - Univ Hlth Sci, Umraniye Training & Res Hosp, Dept Pediat Genet, Istanbul, Turkey
Flore Rozenberg - Assistance Publique – Hôpitaux de Paris
Abderrahmane Errami - University of Hassan II Casablanca
Shen-Ying Zhang - Rockefeller University
Qian Zhang - Rockefeller University
Jonathan Bohlen - Inserm
Anne Puel - Rockefeller University
Emmanuelle Jouanguy - Rockefeller University
Zahra Pourmoghaddas - Isfahan University of Medical Sciences
Shahrzad Bakhtiar - University Hospital Frankfurt
Andre M. Willasch - University Hospital Frankfurt
Gerd Horneff - Asklepios Klinik Sankt Augustin
Genevieve Llanora - National University Health System
Lynette P. Shek - National University Health System
Louis Y. A. Chai - National University Health System
Sen Hee Tay - National University of Singapore
Hamid H. Rahimi - College Station Medical Center
Seyed Alireza Mahdaviani - Shahid Beheshti University of Medical Sciences
Serdar Nepesov - Istanbul Medipol University
Aziz A. Bousfiha - University of Hassan II Casablanca
Emine Hafize Erdeniz - Ondokuz Mayıs University
Adem Karbuz - Okmeydanı Eğitim ve Araştırma Hastanesi
Nico Marr - Qatar Airways
Carmen Navarrete - Hospital Roberto del Rio
Mehdi Adeli - Hamad Medical Corporation
Lennart Hammarstrom - Karolinska Institutet
Hassan Abolhassani - Karolinska Institutet
Nima Parvaneh - Children's Medical Center
Saleh Al Muhsen - King Saud University
Mohammed F. Alosaimi - King Saud University
Fahad Alsohime - King Saud University
Maryam Nourizadeh - Tehran University of Medical Sciences
Mostafa Moin - Tehran University of Medical Sciences
Rand Arnaout - King Faisal Specialist Hospital & Research Centre
Saad Alshareef - King Faisal Specialist Hospital & Research Centre
Jamila El-Baghdadi - Mohamed V Mil Hosp, Genet Unit, Rabat, Morocco
Ferah Genel - University of Health Sciences, Dr Behçet Uz Children's Hospital, Division of Pediatric Immunology, Izmir, Turkey.
Roya Sherkat - Isfahan University of Medical Sciences
Ayca Kiykim - Istanbul University-Cerrahpaşa
Esra Yucel - Istanbul University
Sevgi Keles - Necmettin Erbakan University
Jacinta Bustamante - Rockefeller University
Laurent Abel - Rockefeller University
Jean-Laurent Casanova - Rockefeller University
Stephanie Boisson-Dupuis - Rockefeller University
Publication Details: The Journal of experimental medicine, Vol.219(10)
Publisher: Rockefeller Univ Press
Number of pages: 33
Grant note: Rockefeller University Sidra Medicine SCOR Corporate Foundation for Science CT 8062018/046-2019 / Movilidad Academica ECOS-Nord/MINCIENCIAS, Colombia Stony Wold-Herbert Fund Howard Hughes Medical Institute Square Foundation GAIN 01GM1910A / Bundesministerium fur Bildung und Forschung; Federal Ministry of Education & Research (BMBF) St. Giles Foundation Australian Government Research Training Program Stipend Scholarship; Australian Government Meyer Foundation 111574455633/CT 713-2016; 111584467551/CT 415-2020 / Ministerio de Ciencia Tecnologia e Innovacion MINCIENCIAS, Colombia EXC-21899; 390939984 / Deutsche Forschungsgemeinschaft; German Research Foundation (DFG) Grandir-Fonds de solidarite pour l'enfance, Fondation du Souffle National University Health System, Singapore F99CA274708 / National Cancer Institute F99 Award Immune Deficiency Foundation Fondation du Souffle David Rockefeller Graduate Program Institut National de la Sante et de la Recherche M'edicale, University of Paris 824110 / European Union; European Commission; Spanish Government EQU201903007798 / French Foundation for Medical Research; Fondation pour la Recherche Medicale ANRS-COV05; ECTZ170784 / ANRS; French National Research Agency (ANR) R01AI095983; R01AI163029; U19AI142737; U19AI111143; U19AI162568 / National Institute of Allergy and Infectious Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) ANR-10-LABX-62-IBEID; ANR-20-CE93-003; ANR-16-CE17-0005-01 / Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence REACTing-INSERM Fulbright Future Scholarship Funai Foundation for Information Technology Fisher Center for Alzheimer's Research Foundation UL1TR001866 / National Center for Advancing Sciences of the National Institutes of Health EMBO; European Molecular Biology Organization (EMBO) JPB Foundation National Medical Research Council Singapore; National Medical Research Council, Singapore; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) CT 2017-16003 / Comite para el Desarrollo de la Investigacion, CODI -UdeA, Colombia Honjo International Scholarship Foundation ANR-10-IAHU-01 / French National Research Agency (ANR) under the Investments for the Future program; French National Research Agency (ANR) New York Hideyo Noguchi Memorial Society
Identifiers: 9924243808331
Academic Unit: King Khalid University; King Faisal University; King Saud University; Alfaisal University
Language: English
Resource Type: Journal article