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Visualizing Impairment of the Endothelial and Glial Barriers of the Neurovascular Unit during Experimental Autoimmune Encephalomyelitis In Vivo
Published on: March 26, 2019
Immune landscape of the affected brain in Rasmussen encephalitis.
Giovanni Quinones-Valdez1, Julia W Chang2, Shino D Magaki2
1Department of Integrative Biology and Physiology, College of Life Sciences, University of California Los Angeles, Los Angeles, CA, USA.
Rasmussen encephalitis involves activated microglia and CD8 T cells in the brain. Researchers found no active viruses but did detect transcription of endogenous HERV-K retrovirus sequences.
Area of Science:
- Neuroimmunology
- Neuroinflammation
- Autoimmune Diseases
Background:
- Rasmussen encephalitis (RE) is a rare neuroinflammatory disease causing severe seizures and brain atrophy.
- Current treatments include anti-seizure drugs and immunotherapy, but surgical resection is the only cure.
- Clonally expanded T cells in resected brain tissue suggest an autoimmune basis for RE.
Purpose of the Study:
- To characterize the immune cell landscape in Rasmussen encephalitis brain tissue.
- To investigate potential immune cell crosstalk and viral involvement in RE pathogenesis.
Main Methods:
- Single cell RNA sequencing of immune cells isolated from three RE patient brain samples.
- Multiplex immunofluorescence staining for cellular phenotyping.
- T cell receptor sequencing and viral sequence analysis using ViralTrack software.
Main Results:
- Immune infiltrates were dominated by activated microglia and resident memory CD8 T cells.
- CD8 T cells showed markers of activation and exhaustion, with a virus-responsive gene signature.
- Microglia expressed disease-associated and inflammasome-related transcripts.
- No evidence of active latent viruses was found, but endogenous HERV-K retroviral sequences were transcribed.
Conclusions:
- The immune profile in RE brain tissue suggests a complex interplay between microglia and activated, potentially exhausted, CD8 T cells.
- The transcription of endogenous HERV-K sequences warrants further investigation into their role in RE pathogenesis.
- These findings offer insights into the autoimmune mechanisms underlying Rasmussen encephalitis.
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