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Calnexin is necessary for T cell transmigration into the central nervous system
Joanna Jung, … , Luis B. Agellon, Marek Michalak
Joanna Jung, … , Luis B. Agellon, Marek Michalak
Published March 8, 2018
Citation Information: JCI Insight. 2018;3(5):e98410. https://doi.org/10.1172/jci.insight.98410.
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Research Article Cell biology Neuroscience

Calnexin is necessary for T cell transmigration into the central nervous system

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Abstract

In multiple sclerosis (MS), a demyelinating inflammatory disease of the CNS, and its animal model (experimental autoimmune encephalomyelitis; EAE), circulating immune cells gain access to the CNS across the blood-brain barrier to cause inflammation, myelin destruction, and neuronal damage. Here, we discovered that calnexin, an ER chaperone, is highly abundant in human brain endothelial cells of MS patients. Conversely, mice lacking calnexin exhibited resistance to EAE induction, no evidence of immune cell infiltration into the CNS, and no induction of inflammation markers within the CNS. Furthermore, calnexin deficiency in mice did not alter the development or function of the immune system. Instead, the loss of calnexin led to a defect in brain endothelial cell function that resulted in reduced T cell trafficking across the blood-brain barrier. These findings identify calnexin in brain endothelial cells as a potentially novel target for developing strategies aimed at managing or preventing the pathogenic cascade that drives neuroinflammation and destruction of the myelin sheath in MS.

Authors

Joanna Jung, Paul Eggleton, Alison Robinson, Jessica Wang, Nick Gutowski, Janet Holley, Jia Newcombe, Elzbieta Dudek, Amber M. Paul, Douglas Zochodne, Allison Kraus, Christopher Power, Luis B. Agellon, Marek Michalak

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Figure 1

High abundance of calnexin in acute and chronic lesions in brain of multiple sclerosis patients.

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High abundance of calnexin in acute and chronic lesions in brain of mult...
(A) MRI scans of a patient with multiple sclerosis (MS) demonstrating high-signal white matter lesions on FLAIR (top) and T2-weighted (bottom) sequences. Lesions depicted by arrows. (B) 3,3′-Diaminobenzidine (DAB) nickel chloride staining for calnexin (CANX) in non-MS control (NC), normal-appearing white matter (NAWM) MS brain, acute lesions (acute), subacute lesions (subacute), and chronic lesions together with Oil Red O/hematoxylin staining of parallel 10-μm sections of MS tissue, as previously described (44). Lesions are demarcated by a white lined. Scale bar: 25 μm. (C) FACS analysis of CANX in the isolated human brain endothelial cells. Immunofluorescence staining for calnexin in the blood vessels of (top right) non-MS individual and capillaries located in the acute and chronic lesions of MS patient tissue, as previously described (44).

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