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

Ogishi M, Arias AA, Yang R, Han JE, Zhang P, Rinchai D, Halpern J, Mulwa J, Keating N, Chrabieh M, Lainé C, Seeleuthner Y, Ramírez-Alejo N, Nekooie-Marnany N, Guennoun A, Muller-Fleckenstein I, Fleckenstein B, Kilic SS, Minegishi Y, Ehl S, Kaiser-Labusch P, Kendir-Demirkol Y, Rozenberg F, Errami A, Zhang SY, Zhang Q, Bohlen J, Philippot Q, Puel A, Jouanguy E, Pourmoghaddas Z, Bakhtiar S, Willasch AM, Horneff G, Llanora G, Shek LP, Chai LY, Tay SH, Rahimi HH, Mahdaviani SA, Nepesov S, Bousfiha AA, Erdeniz EH, Karbuz A, Marr N, Navarrete C, Adeli M, Hammarstrom L, Abolhassani H, Parvaneh N, Al-Muhsen S, Alosaimi MF, Alsohime F, Nourizadeh M, Moin M, Arnaout R, Alshareef S, El-Baghdadi J, Genel F, Sherkat R, Kiykim A, Yücel E, Keles S, Bustamante J, Abel L, Casanova JL, Boisson-Dupuis S (2022)

Publication Language: English

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 219

Article Number: e20220094

Journal Issue: 10

DOI: 10.1084/jem.20220094

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.

Authors with CRIS profile

Involved external institutions

Rockefeller University United States (USA) (US) Isfahan University of Medical Sciences (IUMS) / دانشگاه علوم پزشکی و خدمات بهداشتی درمانی اصفهان‎‎ Iran, Islamic Republic of (IR) Shahid Beheshti University of Medical Sciences Iran, Islamic Republic of (IR) Istanbul Medipol University / İstanbul Medipol Üniversitesi Turkey (TR) University Hassan II Casablanca / جامعة الحسن الثانی دارالبیضاء Morocco (MA) Ondokuz Mayıs University Turkey (TR) University of Health Sciences Vientiane / ມະຫາວິທະຍາໄລ ວິທະຍາສາດ ສຸຂະພາບ Lao People's Democratic Republic (LA) Sidra Medical and Research Center Qatar (QA) Bursa Uludağ University / Bursa Uludağ Üniversitesi Turkey (TR) Tokushima University / 国立大学法人 徳島大学 Japan (JP) Universitätsklinikum Freiburg Germany (DE) Klinikverbund Bremen (Gesundheit Nord) Germany (DE) Assistance Publique-Hôpitaux de Paris (AP-HP) France (FR) Institut des maladies génétiques Imagine France (FR) King Saud University (KSU) / جامعة الملك سعود‎‎ Saudi Arabia (SA) Tehran University of Medical Sciences (TUMS) / دانشگاه علوم پزشکی تهران Iran, Islamic Republic of (IR) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Asklepios Kinderklinik Sankt Augustin Germany (DE) National University Health System (NUHS) Singapore (SG) NUS Yong Loo Lin School of Medicine Singapore (SG) Roberto del Rio Children's Hospital Chile (CL) Hamad Medical Corporation Qatar (QA) Karolinska Institute Sweden (SE) King Faisal Specialist Hospital & Research Centre Saudi Arabia (SA) Military Hospital Mohammed V Morocco (MA) Istanbul University Cerrahpaşa / İstanbul Üniversitesi Cerrahpaşa (IUC) Turkey (TR) Istanbul University / İstanbul Üniversitesi Turkey (TR) Necmettin Erbakan Üniversitesi Turkey (TR)

How to cite

APA:

Ogishi, M., Arias, A.A., Yang, R., Han, J.E., Zhang, P., Rinchai, D.,... Boisson-Dupuis, S. (2022). Impaired IL-23-dependent induction of IFN-γ underlies mycobacterial disease in patients with inherited TYK2 deficiency. Journal of Experimental Medicine, 219(10). https://doi.org/10.1084/jem.20220094

MLA:

Ogishi, Masato, et al. "Impaired IL-23-dependent induction of IFN-γ underlies mycobacterial disease in patients with inherited TYK2 deficiency." Journal of Experimental Medicine 219.10 (2022).

BibTeX: Download