The Fabp5/calnexin complex is a prerequisite for sensitization of mice to experimental autoimmune encephalomyelitis

• Published in: The FASEB journal Vol. 34; no. 12; p. 16662
• Main Authors: Paskevicius, Tautvydas, Jung, Joanna, Pujol, Myriam, Eggleton, Paul, Qin, Wenying, Robinson, Alison, Gutowski, Nick, Holley, Janet, Smallwood, Miranda, Newcombe, Jia, Zochodne, Douglas, Chen, Xing-Zhen, Tang, Jingfeng, Kraus, Allison, Michalak, Marek, Agellon, Luis B
• Format: Journal Article
• Language: English
• Published: United States 01.12.2020
• Subjects: Animals; Biological Transport - physiology; Blood-Brain Barrier - metabolism; Brain - metabolism; Calnexin - metabolism; Cell Line; Cell Movement - physiology; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - metabolism; Endothelial Cells - metabolism; Fatty Acid-Binding Proteins - metabolism; Female; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neoplasm Proteins - metabolism; Permeability; blood brain barrier; fatty acid binding protein; calnexin; chaperone; multiple sclerosis
• ISSN: 1530-6860
• DOI: 10.1096/fj.202001539RR

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.