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Single-Cell RNA Sequencing of Tocilizumab-Treated Peripheral Blood Mononuclear Cells as an in vitro Model of Inflammation

COVID-19 has posed a significant threat to global health. Early data has revealed that IL-6, a key regulatory cytokine, plays an important role in the cytokine storm of COVID-19. Multiple trials are therefore looking at the effects of Tocilizumab, an IL-6 receptor antibody that inhibits IL-6 activit...

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Autores principales: Zarinsefat, Arya, Hartoularos, George, Rychkov, Dmitry, Rashmi, Priyanka, Chandran, Sindhu, Vincenti, Flavio, Yee, Chun J., Sarwal, Minnie M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813999/
https://www.ncbi.nlm.nih.gov/pubmed/33469465
http://dx.doi.org/10.3389/fgene.2020.610682
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author Zarinsefat, Arya
Hartoularos, George
Rychkov, Dmitry
Rashmi, Priyanka
Chandran, Sindhu
Vincenti, Flavio
Yee, Chun J.
Sarwal, Minnie M.
author_facet Zarinsefat, Arya
Hartoularos, George
Rychkov, Dmitry
Rashmi, Priyanka
Chandran, Sindhu
Vincenti, Flavio
Yee, Chun J.
Sarwal, Minnie M.
author_sort Zarinsefat, Arya
collection PubMed
description COVID-19 has posed a significant threat to global health. Early data has revealed that IL-6, a key regulatory cytokine, plays an important role in the cytokine storm of COVID-19. Multiple trials are therefore looking at the effects of Tocilizumab, an IL-6 receptor antibody that inhibits IL-6 activity, on treatment of COVID-19, with promising findings. As part of a clinical trial looking at the effects of Tocilizumab treatment on kidney transplant recipients with subclinical rejection, we performed single-cell RNA sequencing of comparing stimulated PBMCs before and after Tocilizumab treatment. We leveraged this data to create an in vitro cytokine storm model, to better understand the effects of Tocilizumab in the presence of inflammation. Tocilizumab-treated cells had reduced expression of inflammatory-mediated genes and biologic pathways, particularly amongst monocytes. These results support the hypothesis that Tocilizumab may hinder the cytokine storm of COVID-19, through a demonstration of biologic impact at the single-cell level.
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spelling pubmed-78139992021-01-18 Single-Cell RNA Sequencing of Tocilizumab-Treated Peripheral Blood Mononuclear Cells as an in vitro Model of Inflammation Zarinsefat, Arya Hartoularos, George Rychkov, Dmitry Rashmi, Priyanka Chandran, Sindhu Vincenti, Flavio Yee, Chun J. Sarwal, Minnie M. Front Genet Genetics COVID-19 has posed a significant threat to global health. Early data has revealed that IL-6, a key regulatory cytokine, plays an important role in the cytokine storm of COVID-19. Multiple trials are therefore looking at the effects of Tocilizumab, an IL-6 receptor antibody that inhibits IL-6 activity, on treatment of COVID-19, with promising findings. As part of a clinical trial looking at the effects of Tocilizumab treatment on kidney transplant recipients with subclinical rejection, we performed single-cell RNA sequencing of comparing stimulated PBMCs before and after Tocilizumab treatment. We leveraged this data to create an in vitro cytokine storm model, to better understand the effects of Tocilizumab in the presence of inflammation. Tocilizumab-treated cells had reduced expression of inflammatory-mediated genes and biologic pathways, particularly amongst monocytes. These results support the hypothesis that Tocilizumab may hinder the cytokine storm of COVID-19, through a demonstration of biologic impact at the single-cell level. Frontiers Media S.A. 2021-01-05 /pmc/articles/PMC7813999/ /pubmed/33469465 http://dx.doi.org/10.3389/fgene.2020.610682 Text en Copyright © 2021 Zarinsefat, Hartoularos, Rychkov, Rashmi, Chandran, Vincenti, Yee and Sarwal. http://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 Genetics
Zarinsefat, Arya
Hartoularos, George
Rychkov, Dmitry
Rashmi, Priyanka
Chandran, Sindhu
Vincenti, Flavio
Yee, Chun J.
Sarwal, Minnie M.
Single-Cell RNA Sequencing of Tocilizumab-Treated Peripheral Blood Mononuclear Cells as an in vitro Model of Inflammation
title Single-Cell RNA Sequencing of Tocilizumab-Treated Peripheral Blood Mononuclear Cells as an in vitro Model of Inflammation
title_full Single-Cell RNA Sequencing of Tocilizumab-Treated Peripheral Blood Mononuclear Cells as an in vitro Model of Inflammation
title_fullStr Single-Cell RNA Sequencing of Tocilizumab-Treated Peripheral Blood Mononuclear Cells as an in vitro Model of Inflammation
title_full_unstemmed Single-Cell RNA Sequencing of Tocilizumab-Treated Peripheral Blood Mononuclear Cells as an in vitro Model of Inflammation
title_short Single-Cell RNA Sequencing of Tocilizumab-Treated Peripheral Blood Mononuclear Cells as an in vitro Model of Inflammation
title_sort single-cell rna sequencing of tocilizumab-treated peripheral blood mononuclear cells as an in vitro model of inflammation
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813999/
https://www.ncbi.nlm.nih.gov/pubmed/33469465
http://dx.doi.org/10.3389/fgene.2020.610682
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