ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions

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, Cornelia Halin

Research output: Contribution to journalArticle

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 languageEnglish
Article number759
Number of pages16
JournalFrontiers in Immunology
Volume10
DOIs
Publication statusPublished - Jan 1 2019

Keywords

  • ALCAM
  • allograft rejection
  • blocking antibody
  • cornea
  • DC migration
  • dendritic Cell (DC)
  • lymphangiogenesis
  • lymphatic vessel

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Willrodt, A. H., Salabarria, A. C., Schineis, P., Ignatova, D., Hunter, M. C., Vranova, M., Golding-Ochsenbein, A. M., Sigmund, E., Romagna, A., Strassberger, V., Fabbi, M., Ferrini, S., Cursiefen, C., Neri, D., Guenova, E., Bock, F., & Halin, C. (2019). ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions. Frontiers in Immunology, 10, [759]. https://doi.org/10.3389/fimmu.2019.00759