Universität zu Köln

Willrodt, Ann-Helen, Salabarria, Ann-Charlott ORCID: 0000-0001-6829-2001, Schineis, Philipp, Ignatova, Desislava, Hunter, Morgan Campbell, Vranova, Martina, Golding-Ochsenbein, Alexandra M., Sigmund, Elena ORCID: 0000-0001-5647-879X, Romagna, Annatina, Strassberger, Verena, Fabbi, Marina, Ferrini, Silvano, Cursiefen, Claus, Neri, Dario, Guenova, Emmanuella ORCID: 0000-0001-5478-8735, Bock, Felix and Halin, Cornelia (2019). ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions. Front. Immunol., 10. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-3224

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Willrodt, Ann-Helen UNSPECIFIED UNSPECIFIED UNSPECIFIED Salabarria, Ann-Charlott UNSPECIFIED orcid.org/0000-0001-6829-2001 UNSPECIFIED Schineis, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Ignatova, Desislava UNSPECIFIED UNSPECIFIED UNSPECIFIED Hunter, Morgan Campbell UNSPECIFIED UNSPECIFIED UNSPECIFIED Vranova, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Golding-Ochsenbein, Alexandra M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sigmund, Elena UNSPECIFIED orcid.org/0000-0001-5647-879X UNSPECIFIED Romagna, Annatina UNSPECIFIED UNSPECIFIED UNSPECIFIED Strassberger, Verena UNSPECIFIED UNSPECIFIED UNSPECIFIED Fabbi, Marina UNSPECIFIED UNSPECIFIED UNSPECIFIED Ferrini, Silvano UNSPECIFIED UNSPECIFIED UNSPECIFIED Cursiefen, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Neri, Dario UNSPECIFIED UNSPECIFIED UNSPECIFIED Guenova, Emmanuella UNSPECIFIED orcid.org/0000-0001-5478-8735 UNSPECIFIED Bock, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Halin, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-150803
DOI:	10.3389/fimmu.2019.00759
Journal or Publication Title:	Front. Immunol.
Volume:	10
Date:	2019
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-3224
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL-ADHESION MOLECULE; DENDRITIC CELLS; ENDOTHELIAL-CELLS; MICE LACKING; T-CELLS; CORNEAL; LYMPHANGIOGENESIS; ANGIOGENESIS; EXPRESSION; BLOCKADE Multiple languages Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15080