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Ligand-receptor interactions of galectin-9 and VISTA suppress human T lymphocyte cytotoxic activity

DOI: 10.3389/fimmu.2020.580557 DOI Help

Authors: Inna M. Yasinska (Universities of Kent and Greenwich) , N. Helge Meyer (University of Oldenburg) , Stephanie Schlichtner (Universities of Kent and Greenwich) , Rohanah Hussain (Diamond Light Source) , Giuliano Siligardi (Diamond Light Source) , Maxwell Casely-Hayford (Universities of Kent and Greenwich) , Walter Fiedler (University Medical Center Hamburg-Eppendorf) , Jasmin Wellbrock (University Medical Center Hamburg-Eppendorf) , Cloe Desmet (European Commission Joint Research Centre) , Luigi Calzolai (Universita’ della Svizzera Italiana (USI)) , Luca Varani (Universita’ della Svizzera Italiana (USI)) , Steffen M. Berger (University of Bern) , Ulrike Raap (University of Oldenburg) , Bernhard F. Gibbs (Universities of Kent and Greenwich; University of Oldenburg) , Elizaveta Fasler-Kan (University of Bern; University Hospital Basel; University of Basel) , Vadim V. Sumbayev (Universities of Kent and Greenwich)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Frontiers In Immunology , VOL 11

State: Published (Approved)
Published: November 2020
Diamond Proposal Number(s): 24509 , 20755 , 21202

Open Access Open Access

Abstract: Acute myeloid leukemia (AML), a blood/bone marrow cancer, is a severe and often fatal malignancy. AML cells are capable of impairing the anti-cancer activities of cytotoxic lymphoid cells. This includes the inactivation of natural killer (NK) cells and killing of T lymphocytes. Here we report for the first time that V-domain Ig-containing suppressor of T cell activation (VISTA), a protein expressed by T cells, recognizes galectin-9 secreted by AML cells as a ligand. Importantly, we found that soluble VISTA released by AML cells enhances the effect of galectin-9, most likely by forming multiprotein complexes on the surface of T cells and possibly creating a molecular barrier. These events cause changes in the plasma membrane potential of T cells leading to activation of granzyme B inside cytotoxic T cells, resulting in apoptosis.

Journal Keywords: Galectin-9; VISTA; T cells; NK cells; acute myeloid leukemia; immune escape

Diamond Keywords: Acute Myeloid Leukemia (AML)

Subject Areas: Biology and Bio-materials

Instruments: B23-Circular Dichroism

Added On: 05/01/2021 08:23


Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Cancer Life Sciences & Biotech

Technical Tags:

Spectroscopy Circular Dichroism (CD)