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Mechanisms by which CD74 Contributes to Traumatic Brain Injury

CD74 导致创伤性脑损伤的机制

基本信息

批准号：
10024091
负责人：
M. Karen Newell Rogers
金额：
$ 40.99万
依托单位：
TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10024091
关键词：
Address Animal Model Animals Anti-Inflammatory Agents Antigen Presentation Antigens Astrocytes Attention Autoimmunity Behavioral Binding Bortezomib Brain Brefeldin A Cathepsins Cell surface Cells Chronic Chronic Headaches Cleaved cell Clinical Cystatins Data Emotional Epilepsy Goals Human Immune Immune response Immune system Impaired cognition Inflammation Inflammatory Response Innate Immune Response Learning Length Lysosomes Mediating Memory Migration Inhibitory Factor Modeling Molecular Mus Nerve Degeneration Nervous System Trauma Neurologic Neurologic Dysfunctions Outcome Pathogenesis Patients Peptides Persons Play Proteins Reporting Role SUI1 gene Signal Transduction Spleen Suggestion Syndrome T-Lymphocyte Therapeutic Time Traumatic Brain Injury adaptive immune response adaptive immunity antigen binding base behavioral outcome disability effective therapy experimental study fluid percussion injury improved improved outcome inhibitor/antagonist neurobehavioral neuroinflammation neuropathology new therapeutic target novel novel therapeutics optimal treatments prevent protein function response treatment strategy

项目摘要

Project Summary/ Abstract Traumatic brain injury (TBI), and the ensuing post-traumatic behavioral and neurological syndromes, are serious clinical problems. Approximately 5 million people in the U.S. are living with the chronic consequences of TBI, and optimal treatment strategies are lacking. We have discovered that specific components of the immune system contribute to neuropathology after a TBI. More specifically, we have discovered that CD74, a protein that functions via unique mechanisms that distinctly contribute to either the innate or the adaptive immune response, can be manipulated to improve neurodegeneration and behavioral outcomes after TBI. Our proposal is based on three primary observations: 1) Our preliminary data implicating full-length CD74 signaling via macrophage migration inhibitory factor (MIF)-binding in the astrocytic response to TBI; 2) Our data indicating that depleting full-length CD74 or antagonizing the proteolytic cleavage product(s) of CD74, class II invariant peptide (CLIP), are anti- inflammatory and neuroprotective after TBI; 3) Recent evidence from human clinical TBI patients and experimental TBI in animal models, showing strong evidence for an adaptive immune response, potentially including autoimmunity. Taken together, these studies are important because: A) they will assess the distinct contributions of CD74 to the innate and adaptive immune responses following TBI; B) they will distinguish between the unique mechanisms of CD74 that contribute to TBI-induced neuropathology and post-traumatic behavioral syndromes; and C) they will determine if targeting specific components of CD74 might be a potential therapeutic strategy following TBI.

项目摘要/摘要