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ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions
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 pote...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473055/ https://www.ncbi.nlm.nih.gov/pubmed/31031759 http://dx.doi.org/10.3389/fimmu.2019.00759 |
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author | Willrodt, Ann-Helen Salabarria, Ann-Charlott Schineis, Philipp Ignatova, Desislava Hunter, Morgan Campbell Vranova, Martina Golding-Ochsenbein, Alexandra M. Sigmund, Elena Romagna, Annatina Strassberger, Verena Fabbi, Marina Ferrini, Silvano Cursiefen, Claus Neri, Dario Guenova, Emmanuella Bock, Felix Halin, Cornelia |
author_facet | Willrodt, Ann-Helen Salabarria, Ann-Charlott Schineis, Philipp Ignatova, Desislava Hunter, Morgan Campbell Vranova, Martina Golding-Ochsenbein, Alexandra M. Sigmund, Elena Romagna, Annatina Strassberger, Verena Fabbi, Marina Ferrini, Silvano Cursiefen, Claus Neri, Dario Guenova, Emmanuella Bock, Felix Halin, Cornelia |
author_sort | Willrodt, Ann-Helen |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6473055 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64730552019-04-26 ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions Willrodt, Ann-Helen Salabarria, Ann-Charlott Schineis, Philipp Ignatova, Desislava Hunter, Morgan Campbell Vranova, Martina Golding-Ochsenbein, Alexandra M. Sigmund, Elena Romagna, Annatina Strassberger, Verena Fabbi, Marina Ferrini, Silvano Cursiefen, Claus Neri, Dario Guenova, Emmanuella Bock, Felix Halin, Cornelia Front Immunol Immunology 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. Frontiers Media S.A. 2019-04-12 /pmc/articles/PMC6473055/ /pubmed/31031759 http://dx.doi.org/10.3389/fimmu.2019.00759 Text en Copyright © 2019 Willrodt, Salabarria, Schineis, Ignatova, Hunter, Vranova, Golding-Ochsenbein, Sigmund, Romagna, Strassberger, Fabbi, Ferrini, Cursiefen, Neri, Guenova, Bock and Halin. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Willrodt, Ann-Helen Salabarria, Ann-Charlott Schineis, Philipp Ignatova, Desislava Hunter, Morgan Campbell Vranova, Martina Golding-Ochsenbein, Alexandra M. Sigmund, Elena Romagna, Annatina Strassberger, Verena Fabbi, Marina Ferrini, Silvano Cursiefen, Claus Neri, Dario Guenova, Emmanuella Bock, Felix Halin, Cornelia ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions |
title | ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions |
title_full | ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions |
title_fullStr | ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions |
title_full_unstemmed | ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions |
title_short | ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions |
title_sort | alcam mediates dc migration through afferent lymphatics and promotes allospecific immune reactions |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473055/ https://www.ncbi.nlm.nih.gov/pubmed/31031759 http://dx.doi.org/10.3389/fimmu.2019.00759 |
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