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Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity

Lookup NU author(s): Dr Mario Abinun

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Abstract

Tyrosine kinase 2 (Tyk2) is a nonreceptor tyrosine kinase that belongs to the Janus kinase (Jak) family. Here we identified a homozygous Tyk2 mutation in a patient who had been clinically diagnosed with hyper-IgE syndrome. This patient showed unusual susceptibility to various microorganisms including virus, fungi, and mycobacteria and suffered from atopic dermatitis with elevated serum IgE. The patient's cells displayed defects in multiple cytokine signaling pathways including those for type 1 interferon (IFN), interleukin (IL)-6, IL-10, IL-12, and IL-23. The cytokine signals were successfully restored by transducing the intact Tyk2 gene. Thus, the Tyk2 deficiency is likely to account for the patient's complex clinical manifestations, including the phenotype of impaired T helper 1 (Th1) differentiation and accelerated Th2 differentiation. This study identifies human Tyk2 deficiency and demonstrates that Tyk2 plays obligatory roles in multiple cytokine signals involved in innate and acquired immunity of humans, which differs substantially from Tyk2 function in mice.


Publication metadata

Author(s): Minegishi Y, Saito M, Morio T, Watanabe K, Agematsu K, Tsuchiya S, Takada H, Hara T, Kawamura N, Ariga T, Kaneko H, Kondo N, Tsuge I, Yachie A, Sakiyama Y, Iwata T, Bessho F, Ohishi T, Joh K, Imai K, Kogawa K, Shinohara M, Fujieda M, Wakiguchi H, Pasic S, Abinun M, Ochs HD, Renner ED, Jansson A, Belohradsky BH, Ayse M, Shimizu N, Mizutani S, Miyawaki T, Nonoyama S, Karasuyama H

Publication type: Article

Publication status: Published

Journal: Immunity

Year: 2006

Volume: 25

Issue: 5

Pages: 745-755

ISSN (print): 1074-7613

ISSN (electronic): 1097-4180

Publisher: Cell Press

URL: http://dx.doi.org/10.1016/j.immuni.2006.09.009

DOI: 10.1016/j.immuni.2006.09.009


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