LncRNA XR_001779380 Primes Epithelial Cells for IFN-γ-Mediated Gene Transcription and Facilitates Age-Dependent Intestinal Antimicrobial Defense

Abstract

Epithelial cells along the mucosal surface provide the front line of defense against luminal pathogen infection in the gastrointestinal tract. These epithelial cells represent an integral component of a highly regulated communication network that can transmit essential signals to cells in the underlying intestinal mucosa that, in turn, serve as targets of mucosal immune mediators.

Cryptosporidium uses CSpV1 to activate host type I interferon and attenuate antiparasitic defenses

“…6a). Consistent with previous reports 24,40 , we Mice (5 days old) were orally inoculated with C. parvum (10 6 oocysts/animal) and ileal epithelium (4 cm from the ileocecal junction) was isolated at 48 h p.i. IFN gene expression was evaluated by RT-qPCR and presented as fold change to uninfected control.…”

“…74104). Transcriptome sequencing and result processing were performed by the BGI Americas Corporation (Cambridge, MA) with DNBSEQ™ sequencing technology platforms as previously reported 40 . The quality of RNA was evaluated with a 2100 Bioanalyzer (Agilent Technologies, USA) and Samples classified as good RNA quality had a similar RNA pattern at visual inspection in the Bioanalyzer, an RNA Integrity Number (RIN) > 7 and a concentration >20 ng/ul.…”

The Long Non-Coding RNA Nostrill Regulates Transcription of Irf7 Through Interaction With NF-κB p65 to Enhance Intestinal Epithelial Defense Against Cryptosporidium parvum

“…LncRNAs are increasingly recognized as critical regulatory molecules with roles in diverse biological processes, including inflammation and host defense ( 40 – 42 ). Prior studies have revealed that lncRNAs, such as NR_033736, NR_045064, and XR_001779380 ( 16 – 18 ), participate in the epithelial antimicrobial defense response against C. parvum , and thus represent potential novel therapeutic targets to bolster intestinal epithelial anti- C. parvum defense as the current FDA approved treatments are only partially effective ( 43 ). Here, we build upon a growing body of evidence for the importance of lncRNAs in intestinal epithelial defense against C. parvum to report that the lncRNA Nostrill, transcribed from the 2500002B13Rik gene locus, is significantly upregulated via the NF-κB signaling pathway following C. parvum infection.…”

“…Molecular mechanisms of gene regulation by lncRNAs include the “guide” or “scaffold” whereby lncRNAs interact with RNA-binding proteins including transcription factors or histone-modifying enzymes, or with larger molecular complexes, and direct them to specific genomic loci to impact target gene expression ( 15 ). Numerous lncRNAs have been previously identified that contribute to the intestinal epithelial inflammatory response and anti-Cryptosporidial defense ( 16 – 18 ). For example, NR_045064 was observed to regulate the expression of inducible nitric oxide synthase (iNOS) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in intestinal epithelial cells in response to C. parvum infection through epigenetic modifications by the p300/WDR5/MLL complex, while a different lncRNA, XR_001779380, interacts with a Stat1/SWI/SNF chromatin remodeling complex to enhance IFN-γ-mediated inflammatory gene transcription ( 17 , 18 ).…”

“…Numerous lncRNAs have been previously identified that contribute to the intestinal epithelial inflammatory response and anti-Cryptosporidial defense ( 16 – 18 ). For example, NR_045064 was observed to regulate the expression of inducible nitric oxide synthase (iNOS) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in intestinal epithelial cells in response to C. parvum infection through epigenetic modifications by the p300/WDR5/MLL complex, while a different lncRNA, XR_001779380, interacts with a Stat1/SWI/SNF chromatin remodeling complex to enhance IFN-γ-mediated inflammatory gene transcription ( 17 , 18 ).…”