The Journal of experimental medicine · 2022

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

СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен

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

Аннотация

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.

Предметные рубрики MeSH

Humans Interferon-gamma Interleukin-23 Job Syndrome TYK2 Kinase

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

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH