Year: 2025
Type: dissertation
Abstract: IFN Interferon gamma IMIDs Immune-mediated inflammatory diseaseIn the last decades, the rise in the incidence of intestinal inflammatory disorders has led to significant advances in the study of their genetics, particularly through GWAS studies and Immunochip technology.These approaches have identified numerous genetic variants associated with immune-mediated intestinal diseases, such as inflammatory bowel disease (IBD) and celiac disease (CeD).Despite these advances in the genetics of these diseases, the origins and the molecular mechanisms underlying these pathologies remain largely unknown.While the majority of studies have focused their attention on the study of coding genes, research on non-coding sequences continues relatively limited.This narrow focus on the non-coding genome may partially explain the incomplete understanding of the genetic factors that drive to the development of these disorders.However, the presence of disease-associated variants in non-coding RNA sequences suggests their involvement in the development and progression of these diseases.LncRNAs are increasingly recognized as key regulators of gene expression, with the potential to modulate gene expression in a tissue-specific and context-dependent manner.The identification and characterization of lncRNAs in the context of immune-mediated diseases, including IBD and CeD, is critical given the increasing evidence of their regulatory roles in these conditions.Despite significant progress in understanding lncRNA functions, their precise contribution in the pathogenesis of these diseases remain largely unexplored.This project aims to fill this knowledge gap, contributing to the identification of novel pathogenic molecular pathways and therapeutic targets.Additionally, RNA modifications represent an emerging area of research, with growing evidences pointing to their potential involvement in various immune diseases, adding a new dimension to genetic regulation.Among these modifications, N6-methyladenosine (m 6 A) is the most abundant internal RNA modification in mammals, and has been implicated in several immune processes, such as T cell differentiation and activation, macrophage polarization, or control of cytokine production.Despite these advances, the precise regulation and biological function of RNA modifications remains unclarified, an only a few studies have explored the connection between m 6 A RNA modifications and immunemediated inflammatory diseases.Against this background, the scope of this thesis includes the identification and functional characterization of candidate lncRNAs associated with gastrointestinal inflammatory diseases (GID), which function could be influenced by an m 6 A peak within the lncRNA.
Author: Rojas Márquez, Henar
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7162610568