Mechanisms by which CD74 Contributes to Traumatic Brain Injury Grant uri icon


  • Project Summary/ !Traumatic brain injuries (TBI), that occur at a rate of greater than 2 million per year, and the serious clinicalproblems that occur after TBI, affect approximately 5 million people in the U.S.! alone. Currently, there are noeffective therapies. We have discovered that the immune system may directly contribute to inflammation anddegeneration of the brain, and behavioral deficits following TBI. More specifically, we found that CD74, aprotein involved in both the innate and adaptive immune responses, may contribute to acute, early and chronicpathologies that result from TBI. The rationale for the current proposal is based on three observations: 1) dataindicating that depleting CD74 is anti-inflammatory a neuroprotective after TBI; 2) evidence from human clinicalTBI patients showing strong evidence of an adaptive immune response after TBI; and 3) Our preliminary datathat implicate CD74 in chronic pathologies after TBI. We seek to revolutionize the understanding of TBI-pathology, and to identify potential targets for therapeutic intervention by testing our overarching hypothesisthat CD74 contributes to the innate and adaptive immune responses following TBI and can be targetedto create novel therapies for treatment. Using our established mouse model of brain injury, the fluidpercussion injury (FPI) model, we propose to test our hypothesis using the following Specific Aims: (1) todeteremine the distinct contributions of full-length CD74, CLIPs, and MHCII, to the innate and adaptive immuneresponses after brain trauma injury, (2) to determine the impacts of these CD74-related mechanisms onneuropathology and behavioral outcomes, and (3) to determine the contributions of activated B and T cellsfollowing TBI.Relevance: Based on the urgent clinical need for treatments following TBI, these studies are importantbecause they have the potential to transform our understanding of the innate and adaptive immune responseafter TBI, and because CD74 may provide a novel therapeutic target for treating TBI and post traumaticbehavioral syndromes.

date/time interval

  • 2019 - 2023