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ID2 inhibits innate antiviral immunity by blocking TBK1- and IKKε-induced activation of IRF3.
- Source :
-
Science signaling [Sci Signal] 2022 Jan 04; Vol. 15 (715), pp. eabh0068. Date of Electronic Publication: 2022 Jan 04. - Publication Year :
- 2022
-
Abstract
- The transcription regulator ID2 plays an essential role in the development and differentiation of immune cells. Here, we report that ID2 also negatively regulates antiviral innate immune responses. During viral infection of human epithelial cells, ID2 bound to TANK-binding kinase 1 (TBK1) and to inhibitor of nuclear factor κB kinase ε (IKKε). These interactions inhibited the recruitment and activation of interferon (IFN) regulatory factor 3 (IRF3) by TBK1 or IKKε, leading to a reduction in the expression of IFN-β1 ( IFNB1 ). IFN-β induced the nuclear export of ID2 to form a negative feedback loop. Knocking out ID2 in human cells enhanced innate immune responses and suppressed infection by different viruses, including SARS-CoV-2. Mice with a myeloid-specific deficiency of ID2 produced more IFN-α in response to viral infection and were more resistant to viral infection than wild-type mice. Our findings not only establish ID2 as a modulator of IRF3 activation induced by TBK1 and/or IKKε but also introduce a mechanism for cross-talk between innate immunity and cell development and differentiation.
- Subjects :
- Animals
Antiviral Agents
Humans
Immunity, Innate
Inhibitor of Differentiation Protein 2
Interferon Regulatory Factor-3 genetics
Interferon Regulatory Factor-3 metabolism
Mice
Phosphorylation
Protein Serine-Threonine Kinases genetics
SARS-CoV-2
COVID-19
I-kappa B Kinase genetics
I-kappa B Kinase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1937-9145
- Volume :
- 15
- Issue :
- 715
- Database :
- MEDLINE
- Journal :
- Science signaling
- Publication Type :
- Academic Journal
- Accession number :
- 34982578
- Full Text :
- https://doi.org/10.1126/scisignal.abh0068