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Macrophage Differentiation and Polarization Regulate the Release of the Immune Checkpoint Protein V-Domain Ig Suppressor of T Cell Activation

Recently, the V-domain immunoglobulin suppressor of T-cell activation (VISTA) was identified as a negative immune checkpoint regulator (NCR) that is mainly expressed in hematopoietic cells. Preclinical studies have shown that VISTA blockade results in impeded tumor growth and improved survival. Neve...

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Autores principales: Noubissi Nzeteu, Gaetan Aime, Schlichtner, Stephanie, David, Sulamith, Ruppenstein, Aylin, Fasler-Kan, Elizaveta, Raap, Ulrike, Sumbayev, Vadim V., Gibbs, Bernhard F., Meyer, N. Helge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132587/
https://www.ncbi.nlm.nih.gov/pubmed/35634346
http://dx.doi.org/10.3389/fimmu.2022.837097
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author Noubissi Nzeteu, Gaetan Aime
Schlichtner, Stephanie
David, Sulamith
Ruppenstein, Aylin
Fasler-Kan, Elizaveta
Raap, Ulrike
Sumbayev, Vadim V.
Gibbs, Bernhard F.
Meyer, N. Helge
author_facet Noubissi Nzeteu, Gaetan Aime
Schlichtner, Stephanie
David, Sulamith
Ruppenstein, Aylin
Fasler-Kan, Elizaveta
Raap, Ulrike
Sumbayev, Vadim V.
Gibbs, Bernhard F.
Meyer, N. Helge
author_sort Noubissi Nzeteu, Gaetan Aime
collection PubMed
description Recently, the V-domain immunoglobulin suppressor of T-cell activation (VISTA) was identified as a negative immune checkpoint regulator (NCR) that is mainly expressed in hematopoietic cells. Preclinical studies have shown that VISTA blockade results in impeded tumor growth and improved survival. Nevertheless, little is known about the physiological role of VISTA expression in macrophages. This study focused on the differential expression of VISTA in human monocytes and macrophages in order to elucidate a putative role of VISTA regulation upon macrophage polarization and activation. We observed that human peripheral monocytes constitutively release soluble VISTA, which was regulated via matrix metalloproteinases. However, monocyte stimulation with cytokines that induce macrophage differentiation, such as granulocyte-macrophage colony–stimulating (GM-CSF) and macrophage colony-stimulating factor (M-CSF), substantially reduced soluble VISTA release. VISTA release was further affected by various pro- and anti-inflammatory stimuli that led to macrophage polarization, where activated M1 macrophages generally released more VISTA than M2 macrophages. Additionally, we observed that stimulation of activated macrophages with the toll-like receptor 4 ligand lipopolysaccharide (LPS) led to a further decrease of soluble VISTA release. Moreover, we found that soluble VISTA impairs T cell cytotoxic activity but did not induce their programmed death. Our results suggest that VISTA is constantly produced and released in the peripheral blood where it may contribute to peripheral tolerance.
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spelling pubmed-91325872022-05-26 Macrophage Differentiation and Polarization Regulate the Release of the Immune Checkpoint Protein V-Domain Ig Suppressor of T Cell Activation Noubissi Nzeteu, Gaetan Aime Schlichtner, Stephanie David, Sulamith Ruppenstein, Aylin Fasler-Kan, Elizaveta Raap, Ulrike Sumbayev, Vadim V. Gibbs, Bernhard F. Meyer, N. Helge Front Immunol Immunology Recently, the V-domain immunoglobulin suppressor of T-cell activation (VISTA) was identified as a negative immune checkpoint regulator (NCR) that is mainly expressed in hematopoietic cells. Preclinical studies have shown that VISTA blockade results in impeded tumor growth and improved survival. Nevertheless, little is known about the physiological role of VISTA expression in macrophages. This study focused on the differential expression of VISTA in human monocytes and macrophages in order to elucidate a putative role of VISTA regulation upon macrophage polarization and activation. We observed that human peripheral monocytes constitutively release soluble VISTA, which was regulated via matrix metalloproteinases. However, monocyte stimulation with cytokines that induce macrophage differentiation, such as granulocyte-macrophage colony–stimulating (GM-CSF) and macrophage colony-stimulating factor (M-CSF), substantially reduced soluble VISTA release. VISTA release was further affected by various pro- and anti-inflammatory stimuli that led to macrophage polarization, where activated M1 macrophages generally released more VISTA than M2 macrophages. Additionally, we observed that stimulation of activated macrophages with the toll-like receptor 4 ligand lipopolysaccharide (LPS) led to a further decrease of soluble VISTA release. Moreover, we found that soluble VISTA impairs T cell cytotoxic activity but did not induce their programmed death. Our results suggest that VISTA is constantly produced and released in the peripheral blood where it may contribute to peripheral tolerance. Frontiers Media S.A. 2022-05-11 /pmc/articles/PMC9132587/ /pubmed/35634346 http://dx.doi.org/10.3389/fimmu.2022.837097 Text en Copyright © 2022 Noubissi Nzeteu, Schlichtner, David, Ruppenstein, Fasler-Kan, Raap, Sumbayev, Gibbs and Meyer https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Noubissi Nzeteu, Gaetan Aime
Schlichtner, Stephanie
David, Sulamith
Ruppenstein, Aylin
Fasler-Kan, Elizaveta
Raap, Ulrike
Sumbayev, Vadim V.
Gibbs, Bernhard F.
Meyer, N. Helge
Macrophage Differentiation and Polarization Regulate the Release of the Immune Checkpoint Protein V-Domain Ig Suppressor of T Cell Activation
title Macrophage Differentiation and Polarization Regulate the Release of the Immune Checkpoint Protein V-Domain Ig Suppressor of T Cell Activation
title_full Macrophage Differentiation and Polarization Regulate the Release of the Immune Checkpoint Protein V-Domain Ig Suppressor of T Cell Activation
title_fullStr Macrophage Differentiation and Polarization Regulate the Release of the Immune Checkpoint Protein V-Domain Ig Suppressor of T Cell Activation
title_full_unstemmed Macrophage Differentiation and Polarization Regulate the Release of the Immune Checkpoint Protein V-Domain Ig Suppressor of T Cell Activation
title_short Macrophage Differentiation and Polarization Regulate the Release of the Immune Checkpoint Protein V-Domain Ig Suppressor of T Cell Activation
title_sort macrophage differentiation and polarization regulate the release of the immune checkpoint protein v-domain ig suppressor of t cell activation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132587/
https://www.ncbi.nlm.nih.gov/pubmed/35634346
http://dx.doi.org/10.3389/fimmu.2022.837097
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