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Murine lupus is neutrophil elastase-independent in the MRL.Fas(lpr) model
Loss of tolerance to nuclear antigens and multisystem tissue destruction is a hallmark of systemic lupus erythematosus (SLE). Although the source of autoantigen in lupus remains elusive, a compelling hypothetical source is dead cell debris that drives autoimmune activation. Prior reports suggest tha...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122749/ https://www.ncbi.nlm.nih.gov/pubmed/32243431 http://dx.doi.org/10.1371/journal.pone.0226396 |
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author | Gordon, Rachael A. Tilstra, Jeremy S. Marinov, Anthony Nickerson, Kevin M. Bastacky, Sheldon I. Shlomchik, Mark J. |
author_facet | Gordon, Rachael A. Tilstra, Jeremy S. Marinov, Anthony Nickerson, Kevin M. Bastacky, Sheldon I. Shlomchik, Mark J. |
author_sort | Gordon, Rachael A. |
collection | PubMed |
description | Loss of tolerance to nuclear antigens and multisystem tissue destruction is a hallmark of systemic lupus erythematosus (SLE). Although the source of autoantigen in lupus remains elusive, a compelling hypothetical source is dead cell debris that drives autoimmune activation. Prior reports suggest that neutrophil extracellular traps (NETs) and their associated death pathway, NETosis, are sources of autoantigen in SLE. However, others and we have shown that inhibition of NETs by targeting the NADPH oxidase complex and peptidylarginine deiminase 4 (PADI4) did not ameliorate disease in spontaneous murine models of SLE. Furthermore, myeloperoxidase and PADI4 deletion did not inhibit induced lupus. Since NET formation may occur independently of any one mediator, to address this controversy, we genetically deleted an additional important mediator of NETs and neutrophil effector function, neutrophil elastase (ELANE), in the MRL.Fas(lpr) model of SLE. ELANE deficiency, and by extension ELANE-dependent NETs, had no effect on SLE nephritis, dermatitis, anti-self response, or immune composition in MRL.Fas(lpr) mice. Taken together with prior data from our group and others, these data further challenge the paradigm that NETs and neutrophils are pathogenic in SLE. |
format | Online Article Text |
id | pubmed-7122749 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-71227492020-04-09 Murine lupus is neutrophil elastase-independent in the MRL.Fas(lpr) model Gordon, Rachael A. Tilstra, Jeremy S. Marinov, Anthony Nickerson, Kevin M. Bastacky, Sheldon I. Shlomchik, Mark J. PLoS One Research Article Loss of tolerance to nuclear antigens and multisystem tissue destruction is a hallmark of systemic lupus erythematosus (SLE). Although the source of autoantigen in lupus remains elusive, a compelling hypothetical source is dead cell debris that drives autoimmune activation. Prior reports suggest that neutrophil extracellular traps (NETs) and their associated death pathway, NETosis, are sources of autoantigen in SLE. However, others and we have shown that inhibition of NETs by targeting the NADPH oxidase complex and peptidylarginine deiminase 4 (PADI4) did not ameliorate disease in spontaneous murine models of SLE. Furthermore, myeloperoxidase and PADI4 deletion did not inhibit induced lupus. Since NET formation may occur independently of any one mediator, to address this controversy, we genetically deleted an additional important mediator of NETs and neutrophil effector function, neutrophil elastase (ELANE), in the MRL.Fas(lpr) model of SLE. ELANE deficiency, and by extension ELANE-dependent NETs, had no effect on SLE nephritis, dermatitis, anti-self response, or immune composition in MRL.Fas(lpr) mice. Taken together with prior data from our group and others, these data further challenge the paradigm that NETs and neutrophils are pathogenic in SLE. Public Library of Science 2020-04-03 /pmc/articles/PMC7122749/ /pubmed/32243431 http://dx.doi.org/10.1371/journal.pone.0226396 Text en © 2020 Gordon et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Gordon, Rachael A. Tilstra, Jeremy S. Marinov, Anthony Nickerson, Kevin M. Bastacky, Sheldon I. Shlomchik, Mark J. Murine lupus is neutrophil elastase-independent in the MRL.Fas(lpr) model |
title | Murine lupus is neutrophil elastase-independent in the MRL.Fas(lpr) model |
title_full | Murine lupus is neutrophil elastase-independent in the MRL.Fas(lpr) model |
title_fullStr | Murine lupus is neutrophil elastase-independent in the MRL.Fas(lpr) model |
title_full_unstemmed | Murine lupus is neutrophil elastase-independent in the MRL.Fas(lpr) model |
title_short | Murine lupus is neutrophil elastase-independent in the MRL.Fas(lpr) model |
title_sort | murine lupus is neutrophil elastase-independent in the mrl.fas(lpr) model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122749/ https://www.ncbi.nlm.nih.gov/pubmed/32243431 http://dx.doi.org/10.1371/journal.pone.0226396 |
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