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：
10530689
负责人：
Dimitry N Krementsov
金额：
$ 19.12万
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/10530689
关键词：
Acute Adaptive Immune System Adoptive Transfer Affect Agonist Amino Acids Antibiotics Antibodies Bacterial Infections Biological Response Modifiers Bone Marrow Cell physiology Cell secretion Cells Cessation of life Chimera organism Circulation Code Complementary DNA Complex Cytoplasm Data Disease Drug or chemical Tissue Distribution Effector Cell Endocrine Endotoxemia Endotoxic Shock Endotoxins Exhibits Foundations Gene Expression Genes Genetic Transcription Genome Genomics Golgi Apparatus Hand Health Immune Immune system In Vitro Infectious Agent Inflammation Inflammation Mediators Inflammatory Knockout Mice Kupffer Cells Label Macrophage 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 Shock Signal Pathway Solid Source Stimulus Testing Therapeutic Intervention Tissues Transcript Translations Untranslated RNA arm cecal ligation puncture cell type clinically relevant experimental study gene function genetic element human model immunoregulation in vitro Model in vivo insight microbial novel p38 Mitogen Activated Protein Kinase paracrine polymicrobial sepsis programs reconstitution response therapy development tool

Acute Adaptive Immune System Adoptive Transfer Affect Agonist Amino Acids Antibiotics Antibodies Bacterial Infections Biological Response Modifiers Bone Marrow Cell physiology Cell secretion Cells Cessation of life Chimera organism Circulation Code Complementary DNA Complex Cytoplasm Data Disease Drug or chemical Tissue Distribution Effector Cell Endocrine Endotoxemia Endotoxic Shock Endotoxins Exhibits Foundations Gene Expression Genes Genetic Transcription Genome Genomics Golgi Apparatus Hand Health Immune Immune system In Vitro Infectious Agent Inflammation Inflammation Mediators Inflammatory Knockout Mice Kupffer Cells Label Macrophage 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 Shock Signal Pathway Solid Source Stimulus Testing Therapeutic Intervention Tissues Transcript Translations Untranslated RNA arm cecal ligation puncture cell type clinically relevant experimental study gene function genetic element human model immunoregulation in vitro Model in vivo insight microbial novel p38 Mitogen Activated Protein Kinase paracrine polymicrobial sepsis programs reconstitution response therapy development tool

展开

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.

项目摘要/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关键部门。这些牢房不仅代表了防御的前线微生物，但还介导了自适应免疫系统方向的关键效应子功能。这种效应功能的失调可能会导致致病性炎症和组织损伤，如败血性休克，一种急性疾病，导致三名受影响的患者中的一名死亡。因此，了解这些细胞的功能调节可以帮助开发这种治疗性干预措施疾病。经典蛋白质编码基因代表真核基因组中的遗传因素的少数，然而，这些基因一直是迄今为止绝大多数功能研究的重点，包括研究先天免疫细胞功能。令人惊讶的是，此类基因的数量不会随着生物复杂性，而所谓的非编码基因的数量确实如此。这表明后一个基因执行复杂的单元格特定调节器函数。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剂。我们已经确定了这样的 lncRNA，称为U90926，几乎仅在活化的髓样细胞中表达。该基因的功能是未知。我们已经产生了该基因缺乏的小鼠，我们提出了一个实验计划来在功能上在体外和体内剖析该基因在髓样细胞效应函数中的作用，在临床相关模型中人类炎症性疾病。