A1 Refereed original research article in a scientific journal
CD73 contributes to anti-inflammatory properties of afferent lymphatic endothelial cells in humans and mice
Authors: Eichin Dominik, Pessia Alberto, Takeda Akira, Laakkonen Joni, Bellmann Lydia, Kankainen Matti, Imhof Beat A, Stoitzner Patrizia, Tang Jing, Salmi Marko, Jalkanen Sirpa
Publisher: Wiley
Publication year: 2021
Journal: European Journal of Immunology
Journal name in source: European journal of immunology
Journal acronym: Eur J Immunol
Volume: 51
Issue: 1
First page : 231
Last page: 246
Number of pages: 16
ISSN: 0014-2980
eISSN: 1521-4141
DOI: https://doi.org/10.1002/eji.201948432
Web address : https://doi.org/10.1002/eji.201948432
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/49809718
CD73 is an important ectoenzyme responsible for the production of extracellular adenosine. It is involved in regulating inflammatory responses and cell migration and is overexpressed in various cancers. The functions of CD73 in blood endothelial cells are understood in detail, but its role on afferent lymphatics remains unknown. Moreover, anti-CD73 antibodies are now used in multiple clinical cancer trials, but their effects on different endothelial cell types have not been studied. This study reveals that a previously unknown role of CD73 on afferent lymphatics is to dampen immune responses. Knocking it out or suppressing it by siRNA leads to the upregulation of inflammation-associated genes on lymphatic endothelial cells and a more pro-inflammatory phenotype of interacting dendritic cells in vitro and in vivo. In striking contrast, anti-CD73 antibodies had only negligible effects on the gene expression of lymphatic- and blood-endothelial cells. Our data thus reveal new functions of lymphatic CD73 and indicate a low likelihood of endothelial cell-related adverse effects by CD73 targeting therapeutic antibodies.
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