RNA is taking its Toll: Impact of RNA‐specific Toll‐like receptors on health and disease

Vierbuchen, Tim; Stein, Karina; Heine, Holger

doi:10.1111/all.13680

Cited by 23 publications

(16 citation statements)

References 190 publications

(206 reference statements)

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“…Analysis with the genomic regions enrichment of annotation tool (GREAT) (McLean et al, 2010), performed to identify functional specificities associated with the TLR8-dependent, induced OCT2 peaks, demonstrated that OCT2 peaks are strongly associated with several ontology terms related to the immune responses (as biological process) as well as to viral infection and autoimmune diseases (as disease ontology) (Figure 5E). Therefore, these results are consistent with the presumed biological role of TLR8 (Vierbuchen et al, 2019).…”

Section: Oct2 As a Tf-modulating Gene Expression In Tlr8activated Neutrophilssupporting

confidence: 88%

Induction of OCT2 contributes to regulate the gene expression program in human neutrophils activated via TLR8

et al. 2021

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The transcription factors (TFs) that regulate inducible genes in activated neutrophils are not yet completely characterized. Herein, we show that the genomic distribution of the histone modification H3K27Ac, as well as PU.1 and C/EBPb, two myeloid-lineage-determining TFs (LDTFs), significantly changes in human neutrophils treated with R848, a ligand of Toll-like receptor 8 (TLR8). Interestingly, differentially acetylated and LDTFmarked regions reveal an over-representation of OCT-binding motifs that are selectively bound by OCT2/ POU2F2. Analysis of OCT2 genomic distribution in primary neutrophils and of OCT2-depletion in HL-60differentiated neutrophils proves the requirement for OCT2 in contributing to promote, along with nuclear factor kB (NF-kB) and activator protein 1 (AP-1), the TLR8-induced gene expression program in neutrophils. Altogether, our data demonstrate that neutrophils, upon activation via TLR8, profoundly reprogram their chromatin status, ultimately displaying cell-specific, prolonged transcriptome changes. Data also show an unexpected role for OCT2 in amplifying the transcriptional response to TLR8-mediated activation.

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Section: Oct2 As a Tf-modulating Gene Expression In Tlr8activated Neutrophilssupporting

confidence: 88%

Induction of OCT2 contributes to regulate the gene expression program in human neutrophils activated via TLR8

et al. 2021

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“…TLR7 activation triggers MYD88 intracellular pathway signaling that leads to the activation NFkappa-B and IRF7 to promote the synthesis of inflammatory factors (120) ssRNA ( 121 Calcium ( 138)…”

Section: Cns: Microglia Cells (93)mentioning

confidence: 99%

“…TLR7 and TLR8 are closely related PRRs expressed in endosomal membranes that can detect single-stranded RNA (ssRNA) ( 120 ). Previous works have described the lack of TLR7 expression in IECs, being mainly expressed in plasmacytoid dendritic cells (pDCs), in B cells at the lamina propria ( 122 ), and in the myenteric and submucous plexuses of murine intestine and human ileum ( 104 ).…”

Section: Microbial Pattern Recognition Receptors: Effects On Serotonergic Systemmentioning

confidence: 99%

Crosstalk Between Intestinal Serotonergic System and Pattern Recognition Receptors on the Microbiota–Gut–Brain Axis

et al. 2021

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Disruption of the microbiota–gut–brain axis results in a wide range of pathologies that are affected, from the brain to the intestine. Gut hormones released by enteroendocrine cells to the gastrointestinal (GI) tract are important signaling molecules within this axis. In the search for the language that allows microbiota to communicate with the gut and the brain, serotonin seems to be the most important mediator. In recent years, serotonin has emerged as a key neurotransmitter in the gut–brain axis because it largely contributes to both GI and brain physiology. In addition, intestinal microbiota are crucial in serotonin signaling, which gives more relevance to the role of the serotonin as an important mediator in microbiota–host interactions. Despite the numerous investigations focused on the gut–brain axis and the pathologies associated, little is known regarding how serotonin can mediate in the microbiota–gut–brain axis. In this review, we will mainly discuss serotonergic system modulation by microbiota as a pathway of communication between intestinal microbes and the body on the microbiota–gut–brain axis, and we explore novel therapeutic approaches for GI diseases and mental disorders.

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“…Further, it activates IRF5 and induces the production of IFNβ, IL-12p70, and TNF (55). Of note, TLR8 is also reported to sense cytoplasmic microRNAs of both host and pathogen origins (56). Rhinovirus, the causative agent of the common cold is known to repress the expression of TLR8 mRNA (57).…”

Section: Discussionmentioning

confidence: 99%

Computational prediction of SARS-CoV-2 encoded miRNAs and their putative host targets

Verma

Dwivedy

Kumar

et al. 2020

Preprint

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Background: Over the past two decades, there has been a continued research on the role of small non-coding RNAs including microRNAs (miRNAs) in various diseases. Studies have shown that viruses modulate the host cellular machinery and hijack its metabolic and immune signaling pathways by miRNA mediated gene silencing. Given the immensity of coronavirus disease 19 (COVID-19) pandemic and the strong association of viral encoded miRNAs with their pathogenesis, it is important to study Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) miRNAs. Results: To address this unexplored area, we identified 8 putative novel miRNAs from SARS-CoV-2 genome and explored their possible human gene targets. A significant proportion of these targets populated key immune and metabolic pathways such as MAPK signaling pathway, maturity-onset diabetes of the young, Insulin signaling pathway, endocytosis, RNA transport, TGF-β signaling pathway, to name a few. The data from this work is backed up by recently reported high-throughput transcriptomics datasets obtains from SARS-CoV-2 infected samples. Analysis of these datasets reveal that a significant proportion of the target human genes were down-regulated upon SARS-CoV-2 infection. Conclusions: The current study brings to light probable host metabolic and immune pathways susceptible to viral miRNA mediated silencing in a SARS-CoV-2 infection, and discusses its effects on the host pathophysiology.

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RNA is taking its Toll: Impact of RNA‐specific Toll‐like receptors on health and disease

Cited by 23 publications

References 190 publications

Induction of OCT2 contributes to regulate the gene expression program in human neutrophils activated via TLR8

Induction of OCT2 contributes to regulate the gene expression program in human neutrophils activated via TLR8

Crosstalk Between Intestinal Serotonergic System and Pattern Recognition Receptors on the Microbiota–Gut–Brain Axis

Computational prediction of SARS-CoV-2 encoded miRNAs and their putative host targets

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