Bacterial expression of a designed single‐chain IL‐10 prevents severe lung inflammation
Abstract 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 lun...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-01-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.202211037 |
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| author | Ariadna Montero‐Blay Javier Delgado Blanco Irene Rodriguez‐Arce Claire Lastrucci Carlos Piñero‐Lambea Maria Lluch‐Senar Luis Serrano |
| author_facet | Ariadna Montero‐Blay Javier Delgado Blanco Irene Rodriguez‐Arce Claire Lastrucci Carlos Piñero‐Lambea Maria Lluch‐Senar Luis Serrano |
| author_sort | Ariadna Montero‐Blay |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-4e63f045fc02418b846daa55c2ead9d6 |
| institution | DOAJ |
| issn | 1744-4292 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-4e63f045fc02418b846daa55c2ead9d62025-08-20T03:06:10ZengSpringer NatureMolecular Systems Biology1744-42922023-01-0119112010.15252/msb.202211037Bacterial expression of a designed single‐chain IL‐10 prevents severe lung inflammationAriadna Montero‐Blay0Javier Delgado Blanco1Irene Rodriguez‐Arce2Claire Lastrucci3Carlos Piñero‐Lambea4Maria Lluch‐Senar5Luis Serrano6Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyAbstract 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.https://doi.org/10.15252/msb.202211037infectioninterleukinlive biotherapeuticsmycoplasmaprotein engineering |
| spellingShingle | Ariadna Montero‐Blay Javier Delgado Blanco Irene Rodriguez‐Arce Claire Lastrucci Carlos Piñero‐Lambea Maria Lluch‐Senar Luis Serrano Bacterial expression of a designed single‐chain IL‐10 prevents severe lung inflammation Molecular Systems Biology infection interleukin live biotherapeutics mycoplasma protein engineering |
| 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 | infection interleukin live biotherapeutics mycoplasma protein engineering |
| url | https://doi.org/10.15252/msb.202211037 |
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