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Bacterial expression of a designed single‐chain IL‐10 prevents severe lung inflammation

Interleukin‐10 (IL‐10) is an anti‐inflammatory cytokine that is active as a swapped domain dimer and is used in bacterial therapy of gut inflammation. IL‐10 can be used as treatment of a wide range of pulmonary diseases. Here we have developed a non‐pathogenic chassis (CV8) of the human lung bacteri...

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Autores principales: Montero‐Blay, Ariadna, Blanco, Javier Delgado, Rodriguez‐Arce, Irene, Lastrucci, Claire, Piñero‐Lambea, Carlos, Lluch‐Senar, Maria, Serrano, Luis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9834763/
https://www.ncbi.nlm.nih.gov/pubmed/36598022
http://dx.doi.org/10.15252/msb.202211037
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author Montero‐Blay, Ariadna
Blanco, Javier Delgado
Rodriguez‐Arce, Irene
Lastrucci, Claire
Piñero‐Lambea, Carlos
Lluch‐Senar, Maria
Serrano, Luis
author_facet Montero‐Blay, Ariadna
Blanco, Javier Delgado
Rodriguez‐Arce, Irene
Lastrucci, Claire
Piñero‐Lambea, Carlos
Lluch‐Senar, Maria
Serrano, Luis
author_sort Montero‐Blay, Ariadna
collection PubMed
description Interleukin‐10 (IL‐10) is an anti‐inflammatory cytokine that is active as a swapped domain dimer and is used in bacterial therapy of gut inflammation. IL‐10 can be used as treatment of a wide range of pulmonary diseases. Here we have developed a non‐pathogenic chassis (CV8) of the human lung bacterium Mycoplasma pneumoniae (MPN) to treat lung diseases. We find that IL‐10 expression by MPN has a limited impact on the lung inflammatory response in mice. To solve these issues, we rationally designed a single‐chain IL‐10 (SC‐IL10) with or without surface mutations, using our protein design software (ModelX and FoldX). As compared to the IL‐10 WT, the designed SC‐IL10 molecules increase the effective expression in MPN four‐fold, and the activity in mouse and human cell lines between 10 and 60 times, depending on the cell line. The SC‐IL10 molecules expressed in the mouse lung by CV8 in vivo have a powerful anti‐inflammatory effect on Pseudomonas aeruginosa lung infection. This rational design strategy could be used to other molecules with immunomodulatory properties used in bacterial therapy.
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spelling pubmed-98347632023-01-24 Bacterial expression of a designed single‐chain IL‐10 prevents severe lung inflammation Montero‐Blay, Ariadna Blanco, Javier Delgado Rodriguez‐Arce, Irene Lastrucci, Claire Piñero‐Lambea, Carlos Lluch‐Senar, Maria Serrano, Luis Mol Syst Biol Article Interleukin‐10 (IL‐10) is an anti‐inflammatory cytokine that is active as a swapped domain dimer and is used in bacterial therapy of gut inflammation. IL‐10 can be used as treatment of a wide range of pulmonary diseases. Here we have developed a non‐pathogenic chassis (CV8) of the human lung bacterium Mycoplasma pneumoniae (MPN) to treat lung diseases. We find that IL‐10 expression by MPN has a limited impact on the lung inflammatory response in mice. To solve these issues, we rationally designed a single‐chain IL‐10 (SC‐IL10) with or without surface mutations, using our protein design software (ModelX and FoldX). As compared to the IL‐10 WT, the designed SC‐IL10 molecules increase the effective expression in MPN four‐fold, and the activity in mouse and human cell lines between 10 and 60 times, depending on the cell line. The SC‐IL10 molecules expressed in the mouse lung by CV8 in vivo have a powerful anti‐inflammatory effect on Pseudomonas aeruginosa lung infection. This rational design strategy could be used to other molecules with immunomodulatory properties used in bacterial therapy. John Wiley and Sons Inc. 2023-01-04 /pmc/articles/PMC9834763/ /pubmed/36598022 http://dx.doi.org/10.15252/msb.202211037 Text en © 2023 The Authors. Published under the terms of the CC BY 4.0 license. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Montero‐Blay, Ariadna
Blanco, Javier Delgado
Rodriguez‐Arce, Irene
Lastrucci, Claire
Piñero‐Lambea, Carlos
Lluch‐Senar, Maria
Serrano, Luis
Bacterial expression of a designed single‐chain IL‐10 prevents severe lung inflammation
title Bacterial expression of a designed single‐chain IL‐10 prevents severe lung inflammation
title_full Bacterial expression of a designed single‐chain IL‐10 prevents severe lung inflammation
title_fullStr Bacterial expression of a designed single‐chain IL‐10 prevents severe lung inflammation
title_full_unstemmed Bacterial expression of a designed single‐chain IL‐10 prevents severe lung inflammation
title_short Bacterial expression of a designed single‐chain IL‐10 prevents severe lung inflammation
title_sort bacterial expression of a designed single‐chain il‐10 prevents severe lung inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9834763/
https://www.ncbi.nlm.nih.gov/pubmed/36598022
http://dx.doi.org/10.15252/msb.202211037
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