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Myelin Oligodendrocyte Glycoprotein MOG35-55 Induced Experimental Autoimmune Encephalomyelitis EAE in C57BL/6 Mice
Published on: April 15, 2014
The Fabp5/calnexin complex is a prerequisite for sensitization of mice to experimental autoimmune encephalomyelitis
Tautvydas Paskevicius1, Joanna Jung1, Myriam Pujol1
1Department of Biochemistry, University of Alberta, Edmonton, AB, Canada.
Abstract:
We previously showed that calnexin (Canx)-deficient mice are desensitized to experimental autoimmune encephalomyelitis (EAE) induction, a model that is frequently used to study inflammatory demyelinating diseases, due to increased resistance of the blood-brain barrier to immune cell transmigration. We also discovered that Fabp5, an abundant cytoplasmic lipid-binding protein found in brain endothelial cells, makes protein-protein contact with the cytoplasmic C-tail domain of Canx. Remarkably, both Canx-deficient and Fabp5-deficient mice commonly manifest resistance to EAE induction. Here, we evaluated the importance of Fabp5/Canx interactions on EAE pathogenesis and on the patency of a model blood-brain barrier to T-cell transcellular migration. The results demonstrate that formation of a complex comprised of Fabp5 and the C-tail domain of Canx dictates the permeability of the model blood-brain barrier to immune cells and is also a prerequisite for EAE pathogenesis.
Insights
The interaction between Fabp5 and calnexin (Canx) is crucial for immune cell entry into the brain, impacting experimental autoimmune encephalomyelitis (EAE) development and blood-brain barrier permeability.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Vascular Biology
Background:
- Calnexin (Canx)-deficient mice show resistance to experimental autoimmune encephalomyelitis (EAE), a model for inflammatory demyelinating diseases.
- Fabp5, a lipid-binding protein in brain endothelial cells, interacts with Canx's C-tail domain.
- Both Canx-deficient and Fabp5-deficient mice exhibit resistance to EAE induction.
Purpose of the Study:
- To investigate the role of Fabp5/Canx interactions in EAE pathogenesis.
- To determine the impact of Fabp5/Canx interactions on blood-brain barrier permeability to T-cell migration.
Main Methods:
- Utilizing mouse models deficient in Canx and Fabp5.
- Assessing EAE induction and severity.
- Evaluating T-cell transcellular migration across a model blood-brain barrier.
Main Results:
- The formation of a complex between Fabp5 and the C-tail of Canx is essential for EAE pathogenesis.
- This Fabp5/Canx complex regulates blood-brain barrier permeability to immune cells.
- Disruption of this interaction confers resistance to EAE.
Conclusions:
- The Fabp5/Canx complex is a critical determinant of blood-brain barrier function in the context of neuroinflammation.
- Targeting the Fabp5/Canx interaction may offer therapeutic strategies for demyelinating diseases like EAE.
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