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Updated: Jan 25, 2026
Blocking Lymph Flow by Suturing Afferent Lymphatic Vessels in Mice
Published on: May 14, 2020
ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions
Ann-Helen Willrodt1, Ann-Charlott Salabarria2, Philipp Schineis1
1Institute of Pharmaceutical Sciences, ETH Zürich, Zurich, Switzerland.
Insights
Researchers developed a novel antibody targeting Activated Leukocyte Cell Adhesion Molecule (ALCAM) to block its function. This ALCAM blockade effectively prevented corneal allograft rejection in mice by inhibiting immune cell migration and blood vessel growth.
Area of Science:
- Immunology
- Cell Biology
- Vascular Biology
Background:
- Activated Leukocyte Cell Adhesion Molecule (ALCAM, CD166) is an immunoglobulin superfamily member involved in T cell activation, leukocyte trafficking, and (lymph)angiogenesis.
- Therapeutic targeting of ALCAM in inflammatory disorders is hindered by the lack of effective blocking antibodies for murine ALCAM.
Purpose of the Study:
- To identify and characterize a monoclonal antibody against murine ALCAM with blocking activity.
- To evaluate the therapeutic potential of ALCAM blockade in immune-mediated inflammatory conditions, specifically corneal allograft rejection.
Main Methods:
- Development and characterization of a high-affinity monoclonal antibody specific for murine ALCAM.
- In vitro assessment of the antibody's effects on T cell activation, dendritic cell (DC) migration, and (lymph)angiogenesis.
- In vivo evaluation of ALCAM blockade in a murine model of corneal allograft rejection.
Main Results:
- The developed antibody effectively reduced in vitro T cell activation and DC migration across lymphatic endothelial cells.
- ALCAM blockade inhibited in vitro and in vivo lymphangiogenesis and reduced DC emigration from human skin explants.
- ALCAM blockade prevented corneal allograft rejection in mice by retaining DCs in the cornea.
Conclusions:
- A novel blocking antibody against murine ALCAM was successfully developed.
- ALCAM blockade demonstrates therapeutic potential for immune-mediated inflammatory diseases, including corneal allograft rejection.
- ALCAM is identified as a promising therapeutic target for human corneal allograft rejection, given its expression in human corneal DCs and lymphatics.
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.
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