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Oxygen-Mediated Suppression of CD8+ T Cell Proliferation by Macrophages: Role of Pharmacological Inhibitors of HIF Degradation

Myeloid cell interactions with cells of the adaptive immune system are an essential aspect of immunity. A key aspect of that interrelationship is its modulation by the microenvironment. Oxygen is known to influence myelosuppression of T cell activation in part via the Hypoxia inducible (HIF) transcr...

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Autores principales: Gojkovic, Milos, Cunha, Pedro P., Darmasaputra, Gabriella S., Barbieri, Laura, Rundqvist, Helene, Veliça, Pedro, Johnson, Randall S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153186/
https://www.ncbi.nlm.nih.gov/pubmed/34054802
http://dx.doi.org/10.3389/fimmu.2021.633586
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author Gojkovic, Milos
Cunha, Pedro P.
Darmasaputra, Gabriella S.
Barbieri, Laura
Rundqvist, Helene
Veliça, Pedro
Johnson, Randall S.
author_facet Gojkovic, Milos
Cunha, Pedro P.
Darmasaputra, Gabriella S.
Barbieri, Laura
Rundqvist, Helene
Veliça, Pedro
Johnson, Randall S.
author_sort Gojkovic, Milos
collection PubMed
description Myeloid cell interactions with cells of the adaptive immune system are an essential aspect of immunity. A key aspect of that interrelationship is its modulation by the microenvironment. Oxygen is known to influence myelosuppression of T cell activation in part via the Hypoxia inducible (HIF) transcription factors. A number of drugs that act on the HIF pathway are currently in clinical use and it is important to evaluate how they act on immune cell function as part of a better understanding of how they will influence patient outcomes. We show here that increased activation of the HIF pathway, either through deletion of the negative regulator of HIF, the von Hippel-Lindau (VHL) gene, in myeloid cells, or through pharmacological inhibitors of VHL-mediated degradation of HIF, potently suppresses T cell proliferation in myeloid cell/T cell culture. These data demonstrate that both pharmacological and genetic activation of HIF in myeloid cells can suppress adaptive cell immune response.
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spelling pubmed-81531862021-05-27 Oxygen-Mediated Suppression of CD8+ T Cell Proliferation by Macrophages: Role of Pharmacological Inhibitors of HIF Degradation Gojkovic, Milos Cunha, Pedro P. Darmasaputra, Gabriella S. Barbieri, Laura Rundqvist, Helene Veliça, Pedro Johnson, Randall S. Front Immunol Immunology Myeloid cell interactions with cells of the adaptive immune system are an essential aspect of immunity. A key aspect of that interrelationship is its modulation by the microenvironment. Oxygen is known to influence myelosuppression of T cell activation in part via the Hypoxia inducible (HIF) transcription factors. A number of drugs that act on the HIF pathway are currently in clinical use and it is important to evaluate how they act on immune cell function as part of a better understanding of how they will influence patient outcomes. We show here that increased activation of the HIF pathway, either through deletion of the negative regulator of HIF, the von Hippel-Lindau (VHL) gene, in myeloid cells, or through pharmacological inhibitors of VHL-mediated degradation of HIF, potently suppresses T cell proliferation in myeloid cell/T cell culture. These data demonstrate that both pharmacological and genetic activation of HIF in myeloid cells can suppress adaptive cell immune response. Frontiers Media S.A. 2021-05-12 /pmc/articles/PMC8153186/ /pubmed/34054802 http://dx.doi.org/10.3389/fimmu.2021.633586 Text en Copyright © 2021 Gojkovic, Cunha, Darmasaputra, Barbieri, Rundqvist, Veliça and Johnson 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
Gojkovic, Milos
Cunha, Pedro P.
Darmasaputra, Gabriella S.
Barbieri, Laura
Rundqvist, Helene
Veliça, Pedro
Johnson, Randall S.
Oxygen-Mediated Suppression of CD8+ T Cell Proliferation by Macrophages: Role of Pharmacological Inhibitors of HIF Degradation
title Oxygen-Mediated Suppression of CD8+ T Cell Proliferation by Macrophages: Role of Pharmacological Inhibitors of HIF Degradation
title_full Oxygen-Mediated Suppression of CD8+ T Cell Proliferation by Macrophages: Role of Pharmacological Inhibitors of HIF Degradation
title_fullStr Oxygen-Mediated Suppression of CD8+ T Cell Proliferation by Macrophages: Role of Pharmacological Inhibitors of HIF Degradation
title_full_unstemmed Oxygen-Mediated Suppression of CD8+ T Cell Proliferation by Macrophages: Role of Pharmacological Inhibitors of HIF Degradation
title_short Oxygen-Mediated Suppression of CD8+ T Cell Proliferation by Macrophages: Role of Pharmacological Inhibitors of HIF Degradation
title_sort oxygen-mediated suppression of cd8+ t cell proliferation by macrophages: role of pharmacological inhibitors of hif degradation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153186/
https://www.ncbi.nlm.nih.gov/pubmed/34054802
http://dx.doi.org/10.3389/fimmu.2021.633586
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