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

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• dc.contributor.author Montero-Blay, Ariadna, 1994-
• dc.contributor.author Delgado Blanco, Javier
• dc.contributor.author Rodriguez-Arce, Irene
• dc.contributor.author Lastrucci, Claire
• dc.contributor.author Piñero-Lambea, Carlos
• dc.contributor.author Lluch-Senar, Maria 1982-
• dc.contributor.author Serrano Pubull, Luis, 1982-
• dc.date.accessioned 2023-02-22T07:21:59Z
• dc.date.available 2023-02-22T07:21:59Z
• dc.date.issued 2023
• dc.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.
• dc.description.sponsorship This work has been supported by the European Research Council (ERC) grant agreement 670216 (MYCOCHASSIS). We also acknowledge the support of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership, the Centro de Excelencia Severo Ochoa, the CERCA Program from the Generalitat de Catalunya, the European Union's Horizon 2020 research and innovation programme under grant agreement 634942 (MycoSynVac). ML-S acknowledges the support of the FEDER project from Instituto Carlos III (ISCIII, Acción Estratégica en Salud 2016; reference CP16/00094). We also acknowledge the staff of CRG/UPF Proteomics Unit who is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) unit and is a member of the ProteoRed PRB3 consortium which is supported by grant PT17/0019 of the PE I + D + i 2013–2016 from the Instituto de Salud Carlos III (ISCIII) and ERDF.
• dc.format.mimetype application/pdf
• dc.identifier.citation Montero-Blay A, Blanco JD, Rodriguez-Arce I, Lastrucci C, Piñero-Lambea C, Lluch-Senar M, Serrano L. Bacterial expression of a designed single-chain IL-10 prevents severe lung inflammation. Mol Syst Biol. 2023 Jan;19(1):e11037. DOI: 10.15252/msb.202211037
• dc.identifier.doi http://dx.doi.org/10.15252/msb.202211037
• dc.identifier.issn 1744-4292
• dc.identifier.uri http://hdl.handle.net/10230/55843
• dc.language.iso eng
• dc.publisher EMBO Press
• dc.relation.ispartof Mol Syst Biol. 2023 Jan;19(1):e11037
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/670216
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/634942
• dc.rights © 2023 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Infection
• dc.subject.keyword Interleukin
• dc.subject.keyword Live biotherapeutics
• dc.subject.keyword Mycoplasma
• dc.subject.keyword Protein engineering
• dc.title Bacterial expression of a designed single-chain IL-10 prevents severe lung inflammation
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion