Impaired Transmigration of Myeloid-Derived Suppressor Cells across Human Sinusoidal Endothelium Is Associated with Decreased Expression of CD13

Research output: Contribution to journalArticle

Authors

  • Yazid J. Resheq
  • Ann-Katrin Menzner
  • Jacobus Bosch
  • Joseph Tickle
  • Annika Wilhelm
  • Gillian Murihead
  • Henning W. Zimmermann
  • Tony Bruns
  • Daniel F. Gilbert
  • Philipp Tripal
  • Andreas Mackensen
  • Christopher Weston

External organisations

  • Department of Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany.
  • Department of Medicine IV, University of Jena, 07743 Jena, Germany.
  • Department of Internal Medicine 5, Hematology/Oncology, University of Erlangen-Nuremberg
  • Imperial College London
  • Institute of Medical Biotechnology, Friedrich-Alexander-University Erlangen-Nuremberg
  • Optical Imaging Centre Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, 91052 Erlangen, Germany.
  • Institute of Immunology and Immunotherapy, Centre for Liver Research and National Institute for Health Research Birmingham Liver Biomedical Research Centre, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.

Abstract

Human monocytic myeloid-derived suppressor cells (MO-MDSCs) within the hepatic compartment suppress inflammation and impair immune surveillance in liver cancer. It is currently not known whether recruitment of MO-MDSCs from blood via hepatic sinusoidal endothelium (HSEC) contributes to their enrichment within the hepatic compartment. We compared the transmigratory potential of MO-MDSCs and monocytes after adhesion to hepatic endothelial monolayers in flow-based assays that mimic in vivo shear stress in the sinusoids. Despite comparable binding to HSEC monolayers, proportionally fewer MO-MDSCs underwent transendothelial migration, indicating that the final steps of extravasation, where actin polymerization plays an important role, are impaired in MO-MDSCs. In this article, we found reduced levels of CD13 on MO-MDSCs, which has recently been reported to control cell motility in monocytes, alongside reduced VLA-4 expression, an integrin predominantly involved in adherence to the apical side of the endothelium. CD13 and VLA-4 blocking and activating Abs were used in flow-based adhesion assays, live-cell imaging of motility, and actin polymerization studies to confirm a role for CD13 in impaired MO-MDSC transmigration. These findings indicate that CD13 significantly contributes to tissue infiltration by MO-MDSCs and monocytes, thereby contributing to the pathogenesis of hepatic inflammation.

Details

Original languageEnglish
Pages (from-to)1672-1681
Number of pages10
JournalJournal of Immunology
Volume199
Issue number5
Publication statusPublished - 1 Sep 2017

Keywords

  • Actins, Antibodies, Blocking, CD13 Antigens, Cell Adhesion, Cell Movement, Cells, Cultured, Down-Regulation, Endothelium, Corneal, Hemochromatosis, Hepatitis, Humans, Integrin alpha4beta1, Liver, Myeloid-Derived Suppressor Cells, Transendothelial and Transepithelial Migration, Journal Article