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LncRNA regulation of Type I IFN signaling in intestinal epithelium

LncRNA 对肠上皮 I 型 IFN 信号传导的调节

基本信息

批准号：
10331247
负责人：
Xian-Ming Chen
金额：
$ 23.55万
依托单位：
RUSH UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-23 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10331247
关键词：
Address Anti-Inflammatory Agents Biochemical Biochemistry Biological Response Modifiers Biology Cell physiology Cells Cellular biology Communication Coupled Cryptosporidium parvum DNA Data Development Effector Cell Epithelial Epithelial Cells Family Feedback Foundations Functional disorder Future Gastrointestinal Physiology Gastrointestinal tract structure Genes Genetic Transcription Goals Health Homeostasis Host Defense Human Immune Immune response Immunity In Vitro Infection Inflammatory Inflammatory Response Injury Interferon Type I Interferon-alpha Interferons Investigation Ligation Mediating Modeling Molecular Molecular Immunology Molecular Virology Morphology Mucosal Immunity Mucous Membrane Mus Natural Immunity Orthologous Gene Outcome Parasites Pathogenicity Play Production Proteins RNA Regulation Research Role Series Signal Pathway Signal Transduction Site Surface Transcript Untranslated RNA adaptive immune response antimicrobial autocrine chemokine cytokine experience gastrointestinal gastrointestinal epithelium immunopathology immunoreaction in vivo insight intestinal epithelium intestinal homeostasis microbial novel novel therapeutic intervention pathogen receptor response

项目摘要

Summary Epithelial cells along the mucosal surface provide the front line of host defense against pathogen infection in the gastrointestinal (GI) tract. These epithelial cells represent an integral component of a highly regulated communication network that can transmit essential signals to cells in the underlying GI mucosa that, in turn, serve as targets of mucosal immune mediators. How intestinal epithelial cells orchestrate GI mucosal defense is still not fully understood. LncRNAs are recently identified long non-coding transcripts that can regulate gene transcription through their interactions with other effect molecules. We have recently identified a panel of lncRNAs that are upregulated in GI epithelial cells following microbial challenge. Specific lncRNAs display a significant suppressive effect on Type I interferon (IFN)-controlled gene transcription in GI epithelial cells. Interestingly, induction of some lncRNAs is controlled by Type I IFN signaling. Given the emerging significance of lncRNAs in regulation of both innate and adaptive immune responses, coupled with the key role of Type I IFN signaling in regulating GI homeostasis, we speculate that lncRNAs may be important regulators in GI physiology and pathophysiology. In this study, we hypothesize that lncRNAs provide negative feedback regulation of Type I IFN signaling through suppression of Type I IFN-controlled gene transcription, consequently contributing to fine-tuning of epithelial cell innate defense against microbial infection. We will use in vitro, ex vivo and in vivo infection models and complementary biochemical, molecular, and morphologic approaches to elucidate the molecular mechanisms by which lncRNAs modulate Type I IFN-mediated gene transcription in GI epithelial cells (Aim 1) and determine the role of lncRNA- mediated feedback regulation of Type I IFN-mediated gene transcription in GI epithelial innate defense (Aim 2). Therefore, this application will explore a novel mechanism for lncRNAs in regulating GI mucosal innate immunity. Elucidating the regulation of key signal pathways in GI epithelial cells by lncRNAs may reveal new insights into the molecular immunology and immunopathology of the GI tract.

总结