IndraLab
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USP18 inhibits Interferon. 86 / 90
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"As we and others have previously demonstrated that the ISG product USP18 suppresses IFN signaling as a form of negative feedback [XREF_BIBR, XREF_BIBR], reduced ISG mRNA translation under reduced nutrient conditions will be accompanied by sustained transcriptional induction of ISGs, resulting in a prolonged IFN response."
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"In addition, protumor interferon-stimulated genes ISG15 and IFIT3 (interferon-induced protein with tetratricopeptide repeats 3), and oncoprotein USP18 (Ubiquitin Specific Peptidase 18), which suppresses IFN responses, were also driven by LTβR-nonclassical signaling, downregulated by nciLT, and diminished in NIK-deficient B16F10 cells (Fig. 5a)."
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"Given that USP18 suppresses type I IFN signaling and that the mutation in Usp18 Ity9 mice lies within the IFNAR2 binding region of USP18, as well as the importance of type I IFN signaling in bacterial infection, we sought to determine if the IFNAR regulatory function of USP18 is compromised in Usp18 Ity9 mice and whether hyperactivation of type I IFN signaling contributes to the pathogenesis of infection."
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"Given that USP18 attenuates the IFN response, we hypothesized that induction of USP18 allowed HIV‐1 to achieve the balance needed to provide the necessary STAT signaling, without too strong an antiviral response.3.3
USP18 deficiency enhances IFN signaling through JAK-STAT pathway."
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"It demonstrates that the action of USP18 is predicted to reduce the amplitude of the IFNα2 dose-response curve much more than the corresponding amplitude of the IFNβ dose-response, in agreement with previously reported experimental results (42) and our own experimental analysis (not shown)."
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"In the liver, the elevated transcription of ISGs includes a number of negative regulators of IFNalpha signalling pathways, such as ubiquitin specific peptidase 18 (USP18), which inhibits further IFN signalling and is thought to contribute to the lack of IFNalpha induced gene induction in treatment nonresponders [XREF_BIBR, XREF_BIBR]."
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"BMP-6, upregulated in iLCs only after incubation with poly(I:C)-EVs, induces interferon-stimulated genes, down-regulates USP18 (a suppressor of interferon signaling) and induces an immediate exit from the cell cycle in epithelial stem cells, all favorable conditions during viral challenge ."
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"As these two signals have been thought to have counter-regulatory roles in psoriasis (39), lower USP18 might promote higher IFN response and thus lower TNF dependence, and vice versa, agreeing with the positive correlation with PASI improvement we observed during the course of etanercept treatment."
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"Whereas ISG15 conjugation has been widely recognized to act antivirally 13, unconjugated ISG15 serves a proviral role by promoting USP18 mediated suppression of type I IFN receptor (IFNAR) signaling XREF_BIBR, XREF_BIBR, XREF_BIBR; this latter function of ISG15 is responsible for over-amplified ISG induction and fortified viral resistance in humans with inherited ISG15 deficiency."
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"While these patients did not exhibit an increased rate of severe viral disease, they exhibited increased susceptibility to tuberculosis and decreased IFN-gamma production, and their cells were depleted of USP18, which served to downregulate type I IFN signaling by blocking the recycling of ISG15 [XREF_BIBR]."
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"Immune regulatory components whose downregulation improves anti-HIV responses include activated leukocyte cell adhesion molecular (ALCAM) , ubiquitin-specific proteinase 18 (USP18) which negatively regulates type I interferon responses and SAMHD1 in macrophages , and miR-146a that represses antiviral cytokine signaling ."