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dc.contributor.author
Willrodt, Ann-Helen
dc.contributor.author
Salabarria, Ann-Charlott
dc.contributor.author
Schineis, Philipp
dc.contributor.author
Ignatova, Desislava
dc.contributor.author
Campbell Hunter, Morgan
dc.contributor.author
Vranova, Martina
dc.contributor.author
Golding-Ochsenbein, Alexandra M.
dc.contributor.author
Sigmund, Elena
dc.contributor.author
Romagna, Annatina
dc.contributor.author
Strassberger, Verena
dc.contributor.author
Fabbi, Marina
dc.contributor.author
Ferrini, Silvano
dc.contributor.author
Cursiefen, Claus
dc.contributor.author
Neri, Dario
dc.contributor.author
Guenova, Emmanuella
dc.contributor.author
Bock, Felix
dc.contributor.author
Halin, Cornelia
dc.date.accessioned
2019-04-23T06:34:16Z
dc.date.available
2019-04-23T03:11:44Z
dc.date.available
2019-04-23T06:34:16Z
dc.date.issued
2019-04
dc.identifier.issn
1664-3224
dc.identifier.other
10.3389/fimmu.2019.00759
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/338876
dc.identifier.doi
10.3929/ethz-b-000338876
dc.description.abstract
Activated leukocyte cell adhesion molecule (ALCAM, CD166) is a cell adhesion molecule of the immunoglobulin superfamily and has been implicated in diverse pathophysiological processes including T cell activation, leukocyte trafficking, and (lymph)angiogenesis. However, exploring the therapeutic potential of ALCAM blockade in immune-mediated inflammatory disorders has been difficult due to the lack of antibodies with blocking activity toward murine ALCAM. In this study, we identified and characterized a monoclonal antibody with high affinity and specificity for murine ALCAM. This antibody reduced in vitro T cell activation induced by antigen-presenting dendritic cells (DCs) as well as (trans)migration of murine DCs across lymphatic endothelial monolayers. Moreover, it reduced emigration of DCs from in vitro-cultured human skin biopsies. Similarly, antibody-based blockade of ALCAM reduced (lymph)angiogenic processes in vitro and decreased developmental lymphangiogenesis in vivo to levels observed in ALCAM-deficient mice. Since corneal allograft rejection is an important medical condition that also involves (lymph)angiogenesis, DC migration and T cell activation, we investigated the therapeutic potential of ALCAM blockade in murine corneal disease. Blocking ALCAM lead to DC retention in corneas and effectively prevented corneal allograft rejection. Considering that we also detected ALCAM expression in human corneal DCs and lymphatics, our findings identify ALCAM as a potential novel therapeutic target in human corneal allograft rejection.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Frontiers Research Foundation
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
ALCAM
en_US
dc.subject
dendritic Cell (DC)
en_US
dc.subject
lymphatic vessel
en_US
dc.subject
lymphangiogenesis
en_US
dc.subject
DC migration
en_US
dc.subject
cornea
en_US
dc.subject
allograft rejection
en_US
dc.subject
blocking antibody
en_US
dc.title
ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2019-04-12
ethz.journal.title
Frontiers in Immunology
ethz.journal.volume
10
en_US
ethz.journal.abbreviated
Front Immunol
ethz.pages.start
759
en_US
ethz.size
16 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.grant
Elucidating the impact of inflammation on lymphatic vessel function and on the induction of adaptive immunity
en_US
ethz.grant
Elucidating the mechanism and the functional significance of leukocyte migration through afferent lymphatic vessels
en_US
ethz.identifier.wos
ethz.publication.place
Lausanne
en_US
ethz.publication.status
published
en_US
ethz.grant.agreementno
138330
ethz.grant.agreementno
156269
ethz.grant.fundername
SNF
ethz.grant.fundername
SNF
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.program
Projektförderung in Biologie und Medizin (Abteilung III)
ethz.grant.program
Projektförderung in Biologie und Medizin (Abteilung III)
ethz.date.deposited
2019-04-23T03:11:45Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2019-04-23T06:34:43Z
ethz.rosetta.lastUpdated
2019-04-23T06:34:43Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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