Excessive negative regulation of type I interferon disrupts viral control in individuals with Down syndrome.
Excessive negative regulation of type I interferon disrupts viral control in individuals with Down syndrome.
复制标题
I型干扰素的过度负调控会破坏唐氏综合症个体的病毒控制。
DOI：
10.1016/j.immuni.2022.09.007
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发表时间：
2022-11-08
期刊：
影响因子：
32.4
通讯作者：
Bogunovic, Dusan
中科院分区：
文献类型：
--
作者：
Malle, Louise;Martin-Fernandez, Marta;Buta, Sofija;Richardson, Ashley;Bush, Douglas;Bogunovic, Dusan
Down syndrome (DS) is typically caused by triplication of chromosome 21. Phenotypically, DS presents with developmental, neurocognitive, and immune features. Epidemiologically, individuals with DS have less frequent viral infection, but when present, these infections lead to more severe disease. The potent antiviral cytokine Type I Interferon (IFN-I) receptor subunits IFNAR1 and IFNAR2 are located on chromosome 21. While increased IFNAR1/2 expression initially caused hyper-sensitivity to IFN-I, it triggered excessive negative feedback. This led to a hypo-response to subsequent IFN-I stimuli and an ensuing viral susceptibility in DS compared to control cells. Upregulation of IFNAR2 expression phenocopied the DS IFN-I dynamics independent of trisomy 21. CD14+ monocytes from individuals with DS exhibited markers of prior IFN-I exposure and had muted responsiveness to ex-vivo IFN-I stimulation. Our findings unveil oscillations of hyper and hypo-response to IFN-I in DS, predisposing to both lower incidence of viral disease and increased infection-related morbidity and mortality. Individuals with Down syndrome have fewer viral infections, but when infected, they suffer from more severe disease. Malle et al. find that triplication of IFNAR1 and IFNAR2, the receptor subunits of the potent antiviral cytokine IFN-I, in DS results in hyper-active IFN-I signaling. The ensuing hyper-induction of IFNAR negative regulators suppresses subsequent IFN-I stimuli and effectively represses further antiviral defenses.
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影响因子：
9.8
作者：
McQuin C;Goodman A;Chernyshev V;Kamentsky L;Cimini BA;Karhohs KW;Doan M;Ding L;Rafelski SM;Thirstrup D;Wiegraebe W;Singh S;Becker T;Caicedo JC;Carpenter AE
通讯作者：
Carpenter AE
DOI：
10.1084/jem.20151529
发表时间：
2016-06-27
期刊：
The Journal of experimental medicine
影响因子：
--
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通讯作者：
Mancini GM
影响因子：
158.5
作者：
Alsohime, Fahad;Martin-Fernandez, Marta;Alangari, Abdullah A.
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Alangari, Abdullah A.
影响因子：
7
作者：
Boisson-Dupuis S;Kong XF;Okada S;Cypowyj S;Puel A;Abel L;Casanova JL
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影响因子：
3.7
作者：
François-Newton V;Magno de Freitas Almeida G;Payelle-Brogard B;Monneron D;Pichard-Garcia L;Piehler J;Pellegrini S;Uzé G
通讯作者：
Uzé G