Impaired IL-23-dependent induction of IFN-gamma underlies mycobacterial disease in patients with inherited TYK2 deficiency
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info:eu-repo/semantics/openAccessAttribution 4.0 Internationalhttps://creativecommons.org/licenses/by/4.0/Tarih
2022Yazar
Ogishi, MasatoAugusto Arias, Andres
Yang, Rui
Han, Ji Eun
Zhang, Peng
Rinchai, Darawan
Halpern, Joshua
Mulwa, Jeanette
Keating, Narelle
Chrabieh, Maya
Laine, Candice
Seeleuthner, Yoann
Ramirez-Alejo, Noe
Nekooie-Marnany, Nioosha
Guennoun, Andrea
Muller-Fleckenstein, Ingrid
Fleckenstein, Bernhard
Kılıç, Sara Şebnem
Minegishi, Yoshiyuki
Ehl, Stephan
Kaiser-Labusch, Petra
Kendir-Demirkol, Yasemin
Rozenberg, Flore
Errami, Abderrahmane
Zhang, Shen-Ying
Zhang, Qian
Bohlen, Jonathan
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
Kıykım, Ayça
Yücel, Esra
Keleş, Sevgi
Bustamante, Jacinta
Abel, Laurent
Casanova, Jean-Laurent
Boisson-Dupuis, Stephanie
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Ogishi, M., Augusto A., A., Yang, R., Han, J. E., Zhang, P., Rinchai, D. ... Boisson-Dupuis, S. (2022). Impaired IL-23-dependent induction of IFN-gamma underlies mycobacterial disease in patients with inherited TYK2 deficiency. Journal of Experimental Medicine, 219(10). https://doi.org/10.1084/jem.20220094Özet
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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Journal of Experimental MedicineCilt
219Sayı
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