ABSTRACT: Effect of blocking the IL-10 receptor on the microglial transcriptomic signature following chronic traumatic brain injury and nasal anti-CD3 treatment
Project description:Investigating the impact of blocking the IL-10 receptor on the gene expression profile of microglia following chronic traumatic brain injury and nasal anti-CD3 treatment.
Project description:Bulk RNA-sequencing was performed to characterize the gene expression profile of microglia at acute and chronic timepoints following traumatic brain injury and nasal anti-CD3 treatment. We further investigated how the chronic microglial transcriptomic profile is modulated following traumatic brain injury and nasal anti-CD3 treatment in female mice with severe TBI, and in male mice with a delayed administration of treatment post-injury.
Project description:Bulk RNA-sequencing was performed to investigate the transcriptomic signature of phagocytic and non-phagocytic microglia following traumatic brain injury and nasal anti-CD3 treatment.
Project description:We performed bulk RNA-sequencing analysis of brain and blood CD4+Foxp3+ Treg cells from sham and injured mice to characterize the gene expression profile of Tregs following traumatic brain injury and nasal anti-CD3 treatment
Project description:IL-10-dependent Treg-microglia crosstalk induced by nasal anti-CD3 mAb ameliorates traumatic brain injury by modulating microglial phagocytosis and neuroinflammation.
Project description:To investigate whether the immunomodulatory effects of nasal anti-CD3 on the microglial transcriptomic profile following TBI is dependent on Tregs, we employed adoptive transfer experiments
Project description:Traumatic brain injury (TBI) triggers neuroinflammatory cascades mediated by microglia, which promotes tissue repair in the short-term. These cascades may exacerbate TBI-induced tissue damage and symptoms in the months to years post-injury. However, the progression of the microglial function across time post-injury and whether this differs between biological sexes is not well understood. In this study, we examined the microglial proteome in the days (3- and 7-days) to 1 month (28 days) after a midline fluid percussion injury (mFPI) in male and female mice using label-free quantitative proteomics. We identified a reduction in microglial proteins involved with clearance of neuronal debris via phagocytosis at 3- and 7-days post-injury. At 28 days post-injury pro-inflammatory proteins were decreased and anti-inflammatory proteins were increased in microglia. These results indicate a reduction in microglial clearance of neuronal debris in the days post-injury with a shift to anti-inflammatory function by 1 month. The changes in the microglial proteome that occurred across time post-injury did not differ between biological sexes. However, we did identify an increase in microglial proteins related to pro-inflammation as well as insulin and estrogen signalling in males compared with female mice that occurred with or without a brain injury. Although microglial response was similar between males and females up to 1 month following TBI, biological sex differences in the basal microglial proteome has implications for the efficacy of treatment strategies targeting the microglial response post-injury.
Project description:Transcriptomic profiling of brain-infiltrating and peripheral CD4+Foxp3+ Tregs following traumatic brain injury and nasal anti-CD3 treatment
