scholarly journals Regulation of the type I interferon genes and interferon-inducible genes. The protein factors of transcription complexes

1999 ◽  
Vol 15 (6) ◽  
pp. 467-480 ◽  
Author(s):  
A. Karpov ◽  
Keyword(s):  
Type I Interferon ◽  
Type I ◽  
Transcription Complexes ◽  
Inducible Genes

scholarly journals The Abstruse Side of Type I Interferon Immunotherapy for COVID-19 Cases with Comorbidities

2021 ◽  
Vol 1 (1) ◽  
pp. 49-59
Author(s):  
Selvakumar Subbian
Keyword(s):  
Infectious Diseases ◽  
Disease Severity ◽  
Type I Interferon ◽  
Host Factors ◽  
Type I ◽  
The Novel ◽  
Inflammatory Drugs ◽  
Precautionary Measures ◽  
Inducible Genes

The Coronavirus Disease-2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has claimed 1.2 million people globally since December 2019. Although the host factors underpinning COVID-19 pathology are not fully understood, type I interferon (IFN-I) response is considered crucial for SARS-CoV-2 pathogenesis. Perturbations in IFN-I signaling and associated interferon-inducible genes (ISG) are among the primary disease severity indicators in COVID-19. Consequently, IFN-I therapy, either alone or in- combination with existing antiviral or anti-inflammatory drugs, is tested in many ongoing clinical trials to reduce COVID-19 mortality. Since signaling by the IFN-I family of molecules regulates host immune response to other infectious and non-infectious diseases, any imbalance in this family of cytokines would impact the clinical outcome of COVID-19, as well as other co-existing diseases. Therefore, it is imperative to evaluate the beneficial-versus-detrimental effects of IFN-I immunotherapy for COVID-19 patients with divergent disease severity and other co-existing conditions. This review article summarizes the role of IFN-I signaling in infectious and non-infectious diseases of humans. It highlights the precautionary measures to be considered before administering IFN-I to COVID-19 patients having other co-existing disorders. Finally, suggestions are proposed to improve IFN-I immunotherapy to COVID-19.

scholarly journals B7–H3 regulates osteoclast differentiation via type I interferon-dependent IDO induction

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Younseo Oh ◽  
Robin Park ◽  
So Yeon Kim ◽  
Sung-ho Park ◽  
Sungsin Jo ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Osteoblast Differentiation ◽  
Type I Interferon ◽  
Osteoclast Differentiation ◽  
Regulatory Function ◽  
Type I ◽  
Type I Ifn ◽  
B7 Family ◽  
Human Osteoclast ◽  
Inducible Genes

AbstractWhile their function, as immune checkpoint molecules, is well known, B7-family proteins also function as regulatory molecules in bone remodeling. B7–H3 is a receptor ligand of the B7 family that functions primarily as a negative immune checkpoint. While the regulatory function of B7–H3 in osteoblast differentiation has been established, its role in osteoclast differentiation remains unclear. Here we show that B7–H3 is highly expressed in mature osteoclasts and that B7–H3 deficiency leads to the inhibition of osteoclastogenesis in human osteoclast precursors (OCPs). High-throughput transcriptomic analyses reveal that B7–H3 inhibition upregulates IFN signaling as well as IFN-inducible genes, including IDO. Pharmacological inhibition of type-I IFN and IDO knockdown leads to reversal of B7–H3-deficiency-mediated osteoclastogenesis suppression. Although synovial-fluid macrophages from rheumatoid-arthritis patients express B7–H3, inhibition of B7–H3 does not affect their osteoclastogenesis. Thus, our findings highlight B7–H3 as a physiologic positive regulator of osteoclast differentiation and implicate type-I IFN–IDO signaling as its downstream mechanism.

Type I interferon is induced by hemolysis and drives antibody-mediated erythrophagocytosis in sickle cell disease

Blood ◽  
2021 ◽  
Author(s):  
Yunfeng Liu ◽  
Mouli Pal ◽  
Weili Bao ◽  
Patricia Shi ◽  
Cheryl Lobo ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Type I Interferon ◽  
Type I ◽  
Cell Disease ◽  
Iκb Kinase ◽  
Inducible Genes ◽  
Classical Monocytes

Patients with sickle cell disease (SCD) suffer from intravascular hemolysis associated vascular injury and tissue damage. Classical monocytes (CMo), which are the most abundant of circulating monocytes, are activated in SCD, but the cause and consequences of activation remain incompletely understood. We found a positive correlation between total plasma heme levels and circulating IFN-α in patients with SCD along with upregulation of the type I Interferon (IFN-I) inducible genes in sort-purified SCD patients' CMo by transcriptome analysis. We demonstrated that hemolysis led to IFN-I expression, predominantly by mouse liver monocyte and macrophages (Mϕ), primarily through Tank kinase binding 1 (TBK1)/IκB kinase-ε (IKKε) but not TLR4. In response to hemolysis-induced IFN-I, mouse CMo migrated to the liver and differentiated into monocyte derived Mϕ, increasing their numbers by 6-fold with acute hemin treatment. Hemolysis-driven IFN-I activity also led to the induction of Fc receptor CD64 expression on monocyte and Mϕ populations, enhancing alloantibody-mediated erythrophagocytosis in SCD both in vivo in mice and in in vitro human cultures. Altogether, these data demonstrate IFN-I response to hemolysis as a novel activation pathway in monocytes and Mϕ in SCD, opening the possibility for development of IFN-I-based diagnostics and therapeutics against alloantibody-mediated erythrophagocytosis.

scholarly journals Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Activates Type I Interferon Signals in Lupus Nephritis

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Leixi Xue ◽  
Lei Liu ◽  
Jun Huang ◽  
Jian Wen ◽  
Ru Yang ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Lupus Nephritis ◽  
Tumor Necrosis ◽  
Renal Damage ◽  
Mononuclear Cells ◽  
Type I Interferon ◽  
Type I ◽  
Type I Ifn ◽  
Inducible Genes ◽  
Necrosis Factor

Type I interferon (IFN) plays a central role in pathogenesis of systemic lupus erythematosus (SLE); tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has been associated with a pathogenic role in lupus nephritis (LN). Thus we investigated whether TWEAK could induce the activation of type I IFN pathway in LN. We examined this in patient-derived peripheral blood mononuclear cells (PBMCs) as well as MRL/lpr mice, a murine LN model. Relative to the control cohorts, MRL/lpr mice showed severe histological changes, high index levels of renal damage, and elevated expression of type I IFN-inducible genes. After shRNA suppression of TWEAK, we observed that renal damage was significantly attenuated and expression of type I IFN-inducible genes was reduced in MRL/lpr mice. In parallel, siRNA of TWEAK also significantly reduced the expression of type I IFN-inducible genes in PBMCs relative to control transfections. In PBMCs, TWEAK stimulation also led to expression of type I IFN-inducible genes. Our results illustrate a novel regulatory role of TWEAK, in which its activity positively regulates type I IFN pathway in LN based on preclinical models. Our findings suggest TWEAK could act as a critical target in preventing renal damage in patients with LN.

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