Regulation of myeloid cell function by a novel putative lncRNA

一种新型推定lncRNA调节骨髓细胞功能

基本信息

批准号：
10372592
负责人：
Dimitry N Krementsov
金额：
$ 23.02万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-11-19 至 2023-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10372592
关键词：
Acute Adaptive Immune System Adoptive Transfer Affect Agonist Amino Acids Antibiotics Antibodies Biological Response Modifiers Blood Circulation Bone Marrow Cell physiology Cells Cessation of life Chimera organism Code Complementary DNA Complex Cytoplasm Data Disease Drug or chemical Tissue Distribution Effector Cell Endocrine Endotoxemia Endotoxic Shock Endotoxins Exhibits Foundations Gene Expression Genes Genome Genomics Golgi Apparatus Hand Health Immune Immune system In Vitro Infectious Agent Inflammation Inflammation Mediators Inflammatory Knockout Mice Kupffer Cells Label Lead Mammals Mediating Messenger RNA Microbe Minority Modeling Molecular Biology Mus Myeloid Cells National Institute of Allergy and Infectious Disease Open Reading Frames Outcome Pathogenicity Pathology Pathway interactions Patients Pattern recognition receptor Peptide Signal Sequences Peptides Phenotype Play Positioning Attribute Pre-Clinical Model Predisposition Process Proteins Quantitative Reverse Transcriptase PCR RNA Recombinants Regulation Resistance Ribosomes Role Septic Shock Signal Pathway Solid Source Stimulus Testing Therapeutic Intervention Tissues Transcript Translations Untranslated RNA arm base cecal ligation puncture cell type clinically relevant experimental study gene function genetic element human model immunoregulation in vitro Model in vivo insight macrophage microbial novel p38 Mitogen Activated Protein Kinase paracrine polymicrobial sepsis reconstitution response therapy development tool

项目摘要

PROJECT SUMMARY/ABSTRACT Understanding the mechanisms that underlie the function and regulation of immune cells in health and disease is critical to developing therapies aimed at modulating their function. Innate immune cells such as macrophages represent a critical arm of the immune system. These cells not only represent the front line of defense against microbes, but also mediate critical effector functions at the direction of the adaptive immune system. Dysregulation of such effector functions can lead to pathogenic inflammation and tissue damage, as seen in septic shock, an acute condition that results in the death in one out of three affected patients. Thus, understanding the functional regulation of these cells can help to develop therapeutic interventions for such diseases. Classical protein coding genes represent the minority of genetic elements in the eukaryotic genome, and yet these genes have been the focus of the vast majority of functional studies to date, including those investigating innate immune cell function. Surprisingly, the number of such genes does not increase with organismal complexity, while the number of so-called non-coding genes does. This suggests that the latter genes execute complex cell type-specific regulator functions. A class of such genes, called long non-coding RNAs (lncRNAs) have recently emerged as critical regulators of immune cell function. We have identified such a lncRNA, called U90926, as almost exclusively expressed in activated myeloid cells. The function of this gene is unknown. We have generated mice deficient in this gene, and we propose an experimental plan to functionally dissect the role of this gene in myeloid cell effector function, both in vitro and in vivo, in clinically relevant models of human inflammatory disease.

项目概要/摘要了解免疫细胞在健康和疾病中的功能和调节的机制对于开发旨在调节其功能的疗法至关重要。先天免疫细胞，例如巨噬细胞代表免疫系统的重要组成部分。这些细胞不仅代表着防御的前线微生物，而且还在适应性免疫系统的指导下介导关键效应功能。这种效应器功能的失调会导致致病性炎症和组织损伤，如感染性休克，一种导致三分之一受影响患者死亡的急性疾病。因此，了解这些细胞的功能调节有助于开发针对此类疾病的治疗干预措施疾病。经典蛋白质编码基因代表真核基因组中的少数遗传元件，然而，迄今为止，这些基因一直是绝大多数功能研究的焦点，包括那些研究先天免疫细胞功能。令人惊讶的是，此类基因的数量并没有随着基因的增加而增加。生物体的复杂性，而所谓的非编码基因的数量则如此。这表明后一个基因执行复杂的细胞类型特异性调节功能。一类这样的基因，称为长非编码RNA （lncRNA）最近已成为免疫细胞功能的关键调节因子。我们已经确定了这样一个 lncRNA，称为 U90926，几乎只在活化的骨髓细胞中表达。该基因的功能是未知。我们已经培育出了缺乏该基因的小鼠，并且我们提出了一个实验计划来功能性地在临床相关模型中，在体外和体内剖析该基因在骨髓细胞效应功能中的作用人类炎症性疾病。