Authors:	Birkner, Katharina Loos, Julia Gollan, René Steffen, Falk Wasser, Beatrice Ruck, Tobias Meuth, Sven G. Zipp, Frauke Bittner, Stefan
Title:	Neuronal ICAM-5 plays a neuroprotective role in progressive neurodegeneration
Online publication date:	10-Jul-2019
Year of first publication:	2019
Language:	english
Abstract:	Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) leading leading to CNS inflammation and neurodegeneration. Current anti-inflammatory drugs have only limited efficacy on progressive neurodegenerative processes underlining the need to understand immune-mediated neuronal injury. Cell adhesion molecules play an important role for immune cell migration migration over the blood-brain barrier whereas their role in mediating potentially harmful contacts between between invading immune cells and neurons is incompletely understood. Here, we assess the role of the the CNS-specific neuronal adhesion molecule ICAM-5 using experimental autoimmune encephalomyelitis (EAE), an animal model of MS. ICAM-5 knockout mice show a more severe EAE disease course in the chronic chronic phase indicating a neuroprotective function of ICAM-5 in progressive neurodegeneration. In agreement agreement with the predominant CNS-specific function of ICAM-5, lymphocyte function-associated antigen antigen 1 (LFA-1)/ICAM-1 contact between antigen-presenting cells and T helper (Th)17 cells in EAE is is not affected by ICAM-5. Strikingly, intrathecal application of the shed soluble form, sICAM-5, ameliorates ameliorates EAE disease symptoms and thus might serve locally as an endogenous neuronal defense mechanism mechanism which is activated upon neuroinflammation in the CNS. In humans, cerebrospinal fluid from patients patients suffering from progressive forms of MS shows decreased sICAM-5 levels, suggesting a lack of of this endogenous protective pathway in these patient groups. Overall, our study points toward a novel novel role of ICAM-5 in CNS autoinflammation in progressive EAE/MS.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-171
URN:	urn:nbn:de:hebis:77-publ-591403
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Frontiers in neurology 10
Pages or article number:	Art. 205
Publisher:	Frontiers Research Foundation
Publisher place:	Lausanne
Issue date:	2019
ISSN:	1664-2295
Publisher URL:	http://dx.doi.org/10.3389/fneur.2019.00205
Publisher DOI:	10.3389/fneur.2019.00205
Appears in collections:	JGU-Publikationen