ALCAM Mediates DC MigrationThrough Afferent Lymphatics andPromotes Allospecific ImmuneReactions

Ann-Helen Willrodt, Ann-Charlott Salabarria, Philipp Schineis, Desislava Ignatova,Morgan Campbell Hunter, Martina Vranova, Alexandra M. Golding-Ochsenbein,Elena Sigmund, Annatina Romagna, Verena Strassberger, Marina Fabbi,Silvano Ferrini , Claus Cursiefen, Dario Neri, Emmanuella Guenova, Felix Bock andCornelia Halin
Source: Frontiers in Immunology
Publication Date: (2019)
Issue: 10: 759
Research Area:
Immunotherapy / Hematology
Molecular Biology
Drug Discovery
Cells used in publication:
T cell, mouse, stim
Species: mouse
Tissue Origin: blood
CHO-S [suspension]
Species: hamster
Tissue Origin: ovarian
Culture Media:


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.