CD73 contributes to anti‐inflammatory properties of afferent lymphatic endothelial cells in humans and mice

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Eichin , D , Pessia , A , Takeda , A , Laakkonen , J , Bellmann , L , Kankainen , M , Imhof , B A , Stoitzner , P , Tang , J , Salmi , M & Jalkanen , S 2021 , ' CD73 contributes to anti‐inflammatory properties of afferent lymphatic endothelial cells in humans and mice ' , European Journal of Immunology , vol. 51 , no. 1 , pp. 231–246 . https://doi.org/10.1002/eji.201948432

Title: CD73 contributes to anti‐inflammatory properties of afferent lymphatic endothelial cells in humans and mice
Author: Eichin, Dominik; Pessia, Alberto; Takeda, Akira; Laakkonen, Joni; Bellmann, Lydia; Kankainen, Matti; Imhof, Beat A.; Stoitzner, Patrizia; Tang, Jing; Salmi, Marko; Jalkanen, Sirpa
Contributor: University of Helsinki, Research Program in Systems Oncology
University of Helsinki, HUSLAB
University of Helsinki, Department of Public Health
Date: 2021-01-12
Language: eng
Number of pages: 16
Belongs to series: European Journal of Immunology
ISSN: 0014-2980
URI: http://hdl.handle.net/10138/329388
Abstract: 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.
Subject: ADENOSINE RECEPTORS
CANCER
CD73
CYTOSCAPE
DATABASE
DENDRITIC CELLS
DIFFERENTIATION
EXPRESSION
LYMPHOCYTES
MATURATION
PHENOTYPE
dendritic cells
lymphatic endothelial cells
siRNA
vascular biology
3111 Biomedicine
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