Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783747088227500032 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8410056 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT donlanalexandran il13isadriverofcovid19severity AT sutherlandtarae il13isadriverofcovid19severity AT mariechelsea il13isadriverofcovid19severity AT preissnersaskia il13isadriverofcovid19severity AT bradleybenjamint il13isadriverofcovid19severity AT carpenterrebeccam il13isadriverofcovid19severity AT sturekjeffreym il13isadriverofcovid19severity AT majenniez il13isadriverofcovid19severity AT moreaugbrett il13isadriverofcovid19severity AT donowitzjeffreyr il13isadriverofcovid19severity AT buckgregorya il13isadriverofcovid19severity AT serranomyrnag il13isadriverofcovid19severity AT burgessstaceyl il13isadriverofcovid19severity AT abhyankarmayureshm il13isadriverofcovid19severity AT muracameron il13isadriverofcovid19severity AT bournephilipe il13isadriverofcovid19severity AT preissnerrobert il13isadriverofcovid19severity AT youngmaryk il13isadriverofcovid19severity AT lyonsgeneviever il13isadriverofcovid19severity AT loombajohannaj il13isadriverofcovid19severity AT ratcliffesarahj il13isadriverofcovid19severity AT poultermelindad il13isadriverofcovid19severity AT mathersamyj il13isadriverofcovid19severity AT dayanthonyj il13isadriverofcovid19severity AT mannbarbaraj il13isadriverofcovid19severity AT allenjudithe il13isadriverofcovid19severity AT petriwilliama il13isadriverofcovid19severity |