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

2.50
Hdl Handle:
http://hdl.handle.net/11287/620631
Title:
Calnexin is necessary for T cell transmigration into the central nervous system.
Authors:
Jung, J.; Eggleton, P.; Robinson, A.; Wang, J.; Gutowski, Nicholas J.; Holley, J.; Newcombe, J.; Dudek, E.; Paul, A. M.; Zochodne, D.; Kraus, A.; Power, C.; Agellon, L. B.; Michalak, M.
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.
Citation:
Calnexin is necessary for T cell transmigration into the central nervous system. 2018, 3 (5) JCI Insight
Publisher:
American Society for Clinical Investigation
Journal:
JCI insight
Issue Date:
8-Mar-2018
URI:
http://hdl.handle.net/11287/620631
DOI:
10.1172/jci.insight.98410
PubMed ID:
29515033
Additional Links:
https://insight.jci.org/articles/view/98410
Note:
This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.
Type:
Journal Article
Language:
en
ISSN:
2379-3708
Appears in Collections:
Neurology; 2018 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorJung, J.en
dc.contributor.authorEggleton, P.en
dc.contributor.authorRobinson, A.en
dc.contributor.authorWang, J.en
dc.contributor.authorGutowski, Nicholas J.en
dc.contributor.authorHolley, J.en
dc.contributor.authorNewcombe, J.en
dc.contributor.authorDudek, E.en
dc.contributor.authorPaul, A. M.en
dc.contributor.authorZochodne, D.en
dc.contributor.authorKraus, A.en
dc.contributor.authorPower, C.en
dc.contributor.authorAgellon, L. B.en
dc.contributor.authorMichalak, M.en
dc.date.accessioned2018-03-09T13:29:08Z-
dc.date.available2018-03-09T13:29:08Z-
dc.date.issued2018-03-08-
dc.identifier.citationCalnexin is necessary for T cell transmigration into the central nervous system. 2018, 3 (5) JCI Insighten
dc.identifier.issn2379-3708-
dc.identifier.pmid29515033-
dc.identifier.doi10.1172/jci.insight.98410-
dc.identifier.urihttp://hdl.handle.net/11287/620631-
dc.description.abstractIn 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.en
dc.language.isoenen
dc.publisherAmerican Society for Clinical Investigationen
dc.relation.urlhttps://insight.jci.org/articles/view/98410en
dc.rightsArchived with thanks to JCI insight. This article is freely available via Open Access.Users are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles under the "fair use" limitations of US copyright law.en
dc.subjectWessex Classification Subject Headings::Neurologyen
dc.titleCalnexin is necessary for T cell transmigration into the central nervous system.en
dc.typeJournal Articleen
dc.identifier.journalJCI insighten
dc.description.noteThis article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.en
dc.type.versionPublisheden

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