FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2520266967> ?p ?o ?g. }

• W2520266967 abstract "Abstract The success of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by acute graft-versus-host disease (GVHD). Improving the procedure depends on identifying the mechanisms that contribute to this damaging T cell reactivity, while preserving graft-versus-leukemia (GVL) activity against hematopoietic malignancies. Tonic type I IFN signaling in BMT recipients and therapeutic application of recombinant IFN-α have been shown to play an important role in defining the balance between GVHD and GVL responses, but the molecular mechanisms inducing this protective response remains unknown. In this regard, pattern recognition receptors (PRRs) that detect cytosolic nucleic acids and lead to the production of large amounts of type I interferons (IFN-α/β) such as the family of RIG-I-like receptors (RLRs) are of particular interest. RLRs, a subfamily of the cytoplasmic DExD/H- box family of helicases, consist of three members: retinoic acid inducible gene I (RIG-I), melanoma differentiation factor 5 (MDA5), and laboratory of genetics and physiology 2 (LGP2). RIG-I senses viral and bacterial RNA to induce the production of type I interferons, proinflammatory cytokines and inflammasome activation. Double-stranded RNA (dsRNA) carrying a 5'-triphosphate (3pRNA) has been identified as the natural ligand for RIG-I and serves as a selective trigger for RIG-I signaling. Although initially characterized as a main regulator for antiviral host defense, mice deficient in components of the RLR and type I IFN signaling pathway develop inflammatory bowel disease (IBD)-related pathologies. Furthermore, patients suffering from IBD show a highly significant downregulation of RIG-I in ileal epithelial cells and in a recent meta-analysis of genome-wide association studies (GWAS) data, IFNAR1 and MDA-5 were identified as primary candidate genes in susceptible loci for IBD. Together, these results indicate that RLRs and type I IFN signaling have important functions in the suppression of IBD by yet ill defined mechanisms. Given that the pathophysiology of GVHD shares several features with inflammatory bowel disease (IBD), we tested the role of the RIG-I pathway in the context of allo-HSCT. We utilized MAVS-deficient mice, which lack a common adapter for RIG-I signaling, as recipients in an MHC-disparate (BALB/c into B6) model of allo-HSCT. Compared to wild-type (WT) B6 mice, MAVS-KO mice receiving allogeneic BM + T cells displayed significantly worse GVHD mortality (Fig.1 A). Given the enhanced GVHD observed in the absence of RIG-I signaling, we hypothesized that selective engagement of RIG-I by 3pRNA (RIG-I ligand) in vivo would protect recipients from GVHD. Using a B6 into BALB/c model we observed that i.v. administration of a selective RIG-I ligand on d-1 significantly reduced mortality, weight loss and intestinal GVHD histopathology (Fig. 1B and data not shown). In addition, the translocation of LPS and microorganisms from the bowel lumen through the damaged intestinal mucosa to the systemic circulation during pre-transplant conditioning represents a crucial step in GVHD pathophysiology. We observed that administration of RIG-I ligand prior to allo-HSCT augmented intestinal barrier function measured by less fluorescence in the serum after FITC-dextran gavage compared to untreated WT recipients (Fig. 1C). Moreover, RIG-I stimulation augmented epithelial regeneration as determined by organoid formation from freshly isolated crypts (Fig. 1D) and inhibited activation of dendritic cells (DCs) during pre-transplant conditioning (Fig. 1E). To investigate the impact of 3pRNA administration during GVT, we used luciferase+ A20 bioluminescence in B6 into BALB/c tumor challenge recipients demonstrating that RIG-I ligands do not limit GVL (data not shown). Taken together, our results (i) uncover a previously unknown role of the RIG-I-MAVS signaling pathway in GVHD and (ii) offer a novel strategy to foster epithelial regeneration and inhibit antigen presentation during pre-transplant conditioning, while maintaining GVL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare." @default.
• W2520266967 created "2016-09-23" @default.
• W2520266967 creator A5000759396 @default.
• W2520266967 creator A5003503263 @default.
• W2520266967 creator A5006320590 @default.
• W2520266967 creator A5016053915 @default.
• W2520266967 creator A5025089795 @default.
• W2520266967 creator A5042748665 @default.
• W2520266967 creator A5052353546 @default.
• W2520266967 creator A5052557430 @default.
• W2520266967 creator A5052598434 @default.
• W2520266967 creator A5065381669 @default.
• W2520266967 creator A5066163473 @default.
• W2520266967 creator A5066200247 @default.
• W2520266967 creator A5071545734 @default.
• W2520266967 creator A5075018006 @default.
• W2520266967 date "2014-12-06" @default.
• W2520266967 modified "2023-09-30" @default.
• W2520266967 title "The Role of the Cytoplasmic RNA Sensor Retinoic Acid Inducible Gene- I (RIG-I) in Allogeneic Stem Cell Transplantation" @default.
• W2520266967 doi "https://doi.org/10.1182/blood.v124.21.3827.3827" @default.
• W2520266967 hasPublicationYear "2014" @default.
• W2520266967 type Work @default.
• W2520266967 sameAs 2520266967 @default.
• W2520266967 citedByCount "1" @default.
• W2520266967 countsByYear W25202669672016 @default.
• W2520266967 crossrefType "journal-article" @default.
• W2520266967 hasAuthorship W2520266967A5000759396 @default.
• W2520266967 hasAuthorship W2520266967A5003503263 @default.
• W2520266967 hasAuthorship W2520266967A5006320590 @default.
• W2520266967 hasAuthorship W2520266967A5016053915 @default.
• W2520266967 hasAuthorship W2520266967A5025089795 @default.
• W2520266967 hasAuthorship W2520266967A5042748665 @default.
• W2520266967 hasAuthorship W2520266967A5052353546 @default.
• W2520266967 hasAuthorship W2520266967A5052557430 @default.
• W2520266967 hasAuthorship W2520266967A5052598434 @default.
• W2520266967 hasAuthorship W2520266967A5065381669 @default.
• W2520266967 hasAuthorship W2520266967A5066163473 @default.
• W2520266967 hasAuthorship W2520266967A5066200247 @default.
• W2520266967 hasAuthorship W2520266967A5071545734 @default.
• W2520266967 hasAuthorship W2520266967A5075018006 @default.
• W2520266967 hasConcept C104317684 @default.
• W2520266967 hasConcept C111289621 @default.
• W2520266967 hasConcept C126322002 @default.
• W2520266967 hasConcept C134474686 @default.
• W2520266967 hasConcept C136449434 @default.
• W2520266967 hasConcept C164027704 @default.
• W2520266967 hasConcept C166703698 @default.
• W2520266967 hasConcept C203014093 @default.
• W2520266967 hasConcept C2776914184 @default.
• W2520266967 hasConcept C2776954689 @default.
• W2520266967 hasConcept C2781121885 @default.
• W2520266967 hasConcept C28328180 @default.
• W2520266967 hasConcept C2911091166 @default.
• W2520266967 hasConcept C502942594 @default.
• W2520266967 hasConcept C54355233 @default.
• W2520266967 hasConcept C67705224 @default.
• W2520266967 hasConcept C71924100 @default.
• W2520266967 hasConcept C86803240 @default.
• W2520266967 hasConcept C8891405 @default.
• W2520266967 hasConcept C95444343 @default.
• W2520266967 hasConceptScore W2520266967C104317684 @default.
• W2520266967 hasConceptScore W2520266967C111289621 @default.
• W2520266967 hasConceptScore W2520266967C126322002 @default.
• W2520266967 hasConceptScore W2520266967C134474686 @default.
• W2520266967 hasConceptScore W2520266967C136449434 @default.
• W2520266967 hasConceptScore W2520266967C164027704 @default.
• W2520266967 hasConceptScore W2520266967C166703698 @default.
• W2520266967 hasConceptScore W2520266967C203014093 @default.
• W2520266967 hasConceptScore W2520266967C2776914184 @default.
• W2520266967 hasConceptScore W2520266967C2776954689 @default.
• W2520266967 hasConceptScore W2520266967C2781121885 @default.
• W2520266967 hasConceptScore W2520266967C28328180 @default.
• W2520266967 hasConceptScore W2520266967C2911091166 @default.
• W2520266967 hasConceptScore W2520266967C502942594 @default.
• W2520266967 hasConceptScore W2520266967C54355233 @default.
• W2520266967 hasConceptScore W2520266967C67705224 @default.
• W2520266967 hasConceptScore W2520266967C71924100 @default.
• W2520266967 hasConceptScore W2520266967C86803240 @default.
• W2520266967 hasConceptScore W2520266967C8891405 @default.
• W2520266967 hasConceptScore W2520266967C95444343 @default.
• W2520266967 hasLocation W25202669671 @default.
• W2520266967 hasOpenAccess W2520266967 @default.
• W2520266967 hasPrimaryLocation W25202669671 @default.
• W2520266967 hasRelatedWork W159372884 @default.
• W2520266967 hasRelatedWork W1997563789 @default.
• W2520266967 hasRelatedWork W2000403951 @default.
• W2520266967 hasRelatedWork W2110414630 @default.
• W2520266967 hasRelatedWork W2124165032 @default.
• W2520266967 hasRelatedWork W2128822579 @default.
• W2520266967 hasRelatedWork W2145030204 @default.
• W2520266967 hasRelatedWork W2150800804 @default.
• W2520266967 hasRelatedWork W2528360263 @default.
• W2520266967 hasRelatedWork W2565846927 @default.
• W2520266967 hasRelatedWork W2582648781 @default.
• W2520266967 hasRelatedWork W2586587512 @default.
• W2520266967 hasRelatedWork W2594472958 @default.
• W2520266967 hasRelatedWork W2734504280 @default.
• W2520266967 hasRelatedWork W2796282781 @default.
• W2520266967 hasRelatedWork W2922069001 @default.
• W2520266967 hasRelatedWork W2980234447 @default.

• next