The cytosolic nucleic acid sensor LRRFIP1 mediates the production of type I interferon via a β-catenin-dependent pathway

Abstract

Intracellular nucleic acid sensors detect microbial RNA and DNA and trigger the production of type I interferon. However, the cytosolic nucleic acid-sensing system remains to be fully identified. Here we show that the cytosolic nucleic acid-binding protein LRRFIP1 contributed to the production of interferon-beta (IFN-beta) induced by vesicular stomatitis virus (VSV) and Listeria monocytogenes in macrophages. LRRFIP1 bound exogenous nucleic acids and increased the expression of IFN-beta induced by both double-stranded RNA and double-stranded DNA. LRRFIP1 interacted with beta-catenin and promoted the activation of beta-catenin, which increased IFN-beta expression by binding to the C-terminal domain of the transcription factor IRF3 and recruiting the acetyltransferase p300 to the IFN-beta enhanceosome via IRF3. Therefore, LRRFIP1 and its downstream partner beta-catenin constitute another coactivator pathway for IRF3-mediated production of type I interferon.

Integrin CD11b Negatively Regulates TLR9-Triggered Dendritic Cell Cross-Priming by Upregulating microRNA-146a

“…Abs specific to phospho-p65 and Notch1 were from Cell Signaling Technology (Danvers, CA). Abs specific to b-actin and HRP-coupled secondary Abs were described previously (31).…”

“…Protein concentrations of the extracts were measured by bicinchoninic acid assay (Pierce). Equal amounts of the proteins were subjected to SDS-PAGE, transferred onto nitrocellulose membranes, and blotted, as described previously (31).…”

MicroRNAs in the regulation of TLR and RIG-I pathways

“…), membrane molecules (CD300F, CD11b, PECAM-1, 20,21 etc. ), endosome/lysosome-localized molecules (Rab7b, 22,23 CLM-3 24 ), gene transcription coactivators (beta-catenin 25 ), antigen-presenting molecules (MHC I and MHC II 26,27 ), and even HSP70, 28 HSP70L1 29 and NGF. 30 Recently, RIG-I signal pathway regulation was extensively investigated; [31][32][33][34] however, the full anti-inflammatory response mechanisms and the precise finetuning of this process still remain incompletely elucidated.…”

NF-κB activation during intradermal DNA vaccination is essential for eliciting tumor protective antigen-specific CTL responses

“…Most DNA-sensing PRR (DAI, IFI16, AIM2, DHX9) signaling pathways converge in the activation and nuclear translocation of NF-κB to drive the expression of proinflammatory transcriptional targets. To investigate the role of this pathway, we used a plasmid encoding the IκBα-super repressor (IκBα-SR), which functions similarly to endogenous IκBα in its ability to bind and protein 16 (IFI16), 12 leucine rich repeat flightless-interacting protein (LRRFIP1), 13 probable ATP-dependent RNA helicase DDX41 14 and RNA polymerase III, 15 which transcribes dsDNA into double stranded RNA leading to RIG-I activation. However, which of these DNA-sensing signaling pathways promotes the maturation of APCs after DNA electroporation leading to the generation of CTL responses is not fully understood, especially for intradermal vaccination.…”