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.
| Original language | English |
|---|---|
| Article number | 759 |
| Number of pages | 16 |
| Journal | Frontiers in Immunology |
| Volume | 10 |
| DOIs | |
| Publication status | Published - Jan 1 2019 |
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Keywords
- ALCAM
- allograft rejection
- blocking antibody
- cornea
- DC migration
- dendritic Cell (DC)
- lymphangiogenesis
- lymphatic vessel
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
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.
In: Frontiers in Immunology, Vol. 10, 759, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions
AU - Willrodt, Ann Helen
AU - Salabarria, Ann Charlott
AU - Schineis, Philipp
AU - Ignatova, Desislava
AU - Hunter, Morgan Campbell
AU - Vranova, Martina
AU - Golding-Ochsenbein, Alexandra M.
AU - Sigmund, Elena
AU - Romagna, Annatina
AU - Strassberger, Verena
AU - Fabbi, Marina
AU - Ferrini, Silvano
AU - Cursiefen, Claus
AU - Neri, Dario
AU - Guenova, Emmanuella
AU - Bock, Felix
AU - Halin, Cornelia
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - ALCAM
KW - allograft rejection
KW - blocking antibody
KW - cornea
KW - DC migration
KW - dendritic Cell (DC)
KW - lymphangiogenesis
KW - lymphatic vessel
UR - http://www.scopus.com/inward/record.url?scp=85065414731&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065414731&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2019.00759
DO - 10.3389/fimmu.2019.00759
M3 - Article
C2 - 31031759
AN - SCOPUS:85065414731
VL - 10
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
M1 - 759
ER -