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IL-13 is a driver of COVID-19 severity

Immune dysregulation is characteristic of the more severe stages of SARS-CoV-2 infection. Understanding the mechanisms by which the immune system contributes to COVID-19 severity may open new avenues to treatment. Here, we report that elevated IL-13 was associated with the need for mechanical ventil...

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Autores principales: Donlan, Alexandra N., Sutherland, Tara E., Marie, Chelsea, Preissner, Saskia, Bradley, Benjamin T., Carpenter, Rebecca M., Sturek, Jeffrey M., Ma, Jennie Z., Moreau, G. Brett, Donowitz, Jeffrey R., Buck, Gregory A., Serrano, Myrna G., Burgess, Stacey L., Abhyankar, Mayuresh M., Mura, Cameron, Bourne, Philip E., Preissner, Robert, Young, Mary K., Lyons, Genevieve R., Loomba, Johanna J., Ratcliffe, Sarah J., Poulter, Melinda D., Mathers, Amy J., Day, Anthony J., Mann, Barbara J., Allen, Judith E., Petri, William A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410056/
https://www.ncbi.nlm.nih.gov/pubmed/34185704
http://dx.doi.org/10.1172/jci.insight.150107
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author Donlan, Alexandra N.
Sutherland, Tara E.
Marie, Chelsea
Preissner, Saskia
Bradley, Benjamin T.
Carpenter, Rebecca M.
Sturek, Jeffrey M.
Ma, Jennie Z.
Moreau, G. Brett
Donowitz, Jeffrey R.
Buck, Gregory A.
Serrano, Myrna G.
Burgess, Stacey L.
Abhyankar, Mayuresh M.
Mura, Cameron
Bourne, Philip E.
Preissner, Robert
Young, Mary K.
Lyons, Genevieve R.
Loomba, Johanna J.
Ratcliffe, Sarah J.
Poulter, Melinda D.
Mathers, Amy J.
Day, Anthony J.
Mann, Barbara J.
Allen, Judith E.
Petri, William A.
author_facet Donlan, Alexandra N.
Sutherland, Tara E.
Marie, Chelsea
Preissner, Saskia
Bradley, Benjamin T.
Carpenter, Rebecca M.
Sturek, Jeffrey M.
Ma, Jennie Z.
Moreau, G. Brett
Donowitz, Jeffrey R.
Buck, Gregory A.
Serrano, Myrna G.
Burgess, Stacey L.
Abhyankar, Mayuresh M.
Mura, Cameron
Bourne, Philip E.
Preissner, Robert
Young, Mary K.
Lyons, Genevieve R.
Loomba, Johanna J.
Ratcliffe, Sarah J.
Poulter, Melinda D.
Mathers, Amy J.
Day, Anthony J.
Mann, Barbara J.
Allen, Judith E.
Petri, William A.
author_sort Donlan, Alexandra N.
collection PubMed
description Immune dysregulation is characteristic of the more severe stages of SARS-CoV-2 infection. Understanding the mechanisms by which the immune system contributes to COVID-19 severity may open new avenues to treatment. Here, we report that elevated IL-13 was associated with the need for mechanical ventilation in 2 independent patient cohorts. In addition, patients who acquired COVID-19 while prescribed Dupilumab, a mAb that blocks IL-13 and IL-4 signaling, had less severe disease. In SARS-CoV-2–infected mice, IL-13 neutralization reduced death and disease severity without affecting viral load, demonstrating an immunopathogenic role for this cytokine. Following anti–IL-13 treatment in infected mice, hyaluronan synthase 1 (Has1) was the most downregulated gene, and accumulation of the hyaluronan (HA) polysaccharide was decreased in the lung. In patients with COVID-19, HA was increased in the lungs and plasma. Blockade of the HA receptor, CD44, reduced mortality in infected mice, supporting the importance of HA as a pathogenic mediator. Finally, HA was directly induced in the lungs of mice by administration of IL-13, indicating a new role for IL-13 in lung disease. Understanding the role of IL-13 and HA has important implications for therapy of COVID-19 and, potentially, other pulmonary diseases. IL-13 levels were elevated in patients with severe COVID-19. In a mouse model of the disease, IL-13 neutralization reduced the disease and decreased lung HA deposition. Administration of IL-13–induced HA in the lung. Blockade of the HA receptor CD44 prevented mortality, highlighting a potentially novel mechanism for IL-13–mediated HA synthesis in pulmonary pathology.
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spelling pubmed-84100562021-09-07 IL-13 is a driver of COVID-19 severity Donlan, Alexandra N. Sutherland, Tara E. Marie, Chelsea Preissner, Saskia Bradley, Benjamin T. Carpenter, Rebecca M. Sturek, Jeffrey M. Ma, Jennie Z. Moreau, G. Brett Donowitz, Jeffrey R. Buck, Gregory A. Serrano, Myrna G. Burgess, Stacey L. Abhyankar, Mayuresh M. Mura, Cameron Bourne, Philip E. Preissner, Robert Young, Mary K. Lyons, Genevieve R. Loomba, Johanna J. Ratcliffe, Sarah J. Poulter, Melinda D. Mathers, Amy J. Day, Anthony J. Mann, Barbara J. Allen, Judith E. Petri, William A. JCI Insight Research Article Immune dysregulation is characteristic of the more severe stages of SARS-CoV-2 infection. Understanding the mechanisms by which the immune system contributes to COVID-19 severity may open new avenues to treatment. Here, we report that elevated IL-13 was associated with the need for mechanical ventilation in 2 independent patient cohorts. In addition, patients who acquired COVID-19 while prescribed Dupilumab, a mAb that blocks IL-13 and IL-4 signaling, had less severe disease. In SARS-CoV-2–infected mice, IL-13 neutralization reduced death and disease severity without affecting viral load, demonstrating an immunopathogenic role for this cytokine. Following anti–IL-13 treatment in infected mice, hyaluronan synthase 1 (Has1) was the most downregulated gene, and accumulation of the hyaluronan (HA) polysaccharide was decreased in the lung. In patients with COVID-19, HA was increased in the lungs and plasma. Blockade of the HA receptor, CD44, reduced mortality in infected mice, supporting the importance of HA as a pathogenic mediator. Finally, HA was directly induced in the lungs of mice by administration of IL-13, indicating a new role for IL-13 in lung disease. Understanding the role of IL-13 and HA has important implications for therapy of COVID-19 and, potentially, other pulmonary diseases. IL-13 levels were elevated in patients with severe COVID-19. In a mouse model of the disease, IL-13 neutralization reduced the disease and decreased lung HA deposition. Administration of IL-13–induced HA in the lung. Blockade of the HA receptor CD44 prevented mortality, highlighting a potentially novel mechanism for IL-13–mediated HA synthesis in pulmonary pathology. American Society for Clinical Investigation 2021-08-09 /pmc/articles/PMC8410056/ /pubmed/34185704 http://dx.doi.org/10.1172/jci.insight.150107 Text en © 2021 Donlan et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Donlan, Alexandra N.
Sutherland, Tara E.
Marie, Chelsea
Preissner, Saskia
Bradley, Benjamin T.
Carpenter, Rebecca M.
Sturek, Jeffrey M.
Ma, Jennie Z.
Moreau, G. Brett
Donowitz, Jeffrey R.
Buck, Gregory A.
Serrano, Myrna G.
Burgess, Stacey L.
Abhyankar, Mayuresh M.
Mura, Cameron
Bourne, Philip E.
Preissner, Robert
Young, Mary K.
Lyons, Genevieve R.
Loomba, Johanna J.
Ratcliffe, Sarah J.
Poulter, Melinda D.
Mathers, Amy J.
Day, Anthony J.
Mann, Barbara J.
Allen, Judith E.
Petri, William A.
IL-13 is a driver of COVID-19 severity
title IL-13 is a driver of COVID-19 severity
title_full IL-13 is a driver of COVID-19 severity
title_fullStr IL-13 is a driver of COVID-19 severity
title_full_unstemmed IL-13 is a driver of COVID-19 severity
title_short IL-13 is a driver of COVID-19 severity
title_sort il-13 is a driver of covid-19 severity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410056/
https://www.ncbi.nlm.nih.gov/pubmed/34185704
http://dx.doi.org/10.1172/jci.insight.150107
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