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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

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.

项目总结/文摘