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http://hdl.handle.net/2445/186085
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DC Field | Value | Language |
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dc.contributor.author | Serrano, Inmaculada | - |
dc.contributor.author | Luque, Ana | - |
dc.contributor.author | Mitjavila Villeró, Francesca | - |
dc.contributor.author | Blom, Anna M. | - |
dc.contributor.author | Rodríguez de Córdoba, Santiago | - |
dc.contributor.author | Vega Fernández, Maria Cristina | - |
dc.contributor.author | Torras Ambròs, Joan | - |
dc.contributor.author | Aran Perramon, Josep M. | - |
dc.date.accessioned | 2022-05-27T11:57:34Z | - |
dc.date.available | 2022-05-27T11:57:34Z | - |
dc.date.issued | 2022-04-25 | - |
dc.identifier.issn | 1664-3224 | - |
dc.identifier.uri | http://hdl.handle.net/2445/186085 | - |
dc.description.abstract | C4b-binding protein (C4BP) is a well-known regulator of the complement system that holds additional and important activities unrelated to complement inhibition. Recently, we have described a novel immunomodulatory activity in the minor C4BP(beta-) isoform directly acting over inflammatory phagocytes. Here we show that incorporation of the beta-chain to the C4BP alpha-chain oligomer interferes with this immunomodulatory activity of C4BP. Moreover, an oligomeric form including only the complement control protein 6 (CCP6) domain of the C4BP alpha-chain (PRP6-HO7) is sufficient to reprogram monocyte-derived DCs (Mo-DCs) from a pro-inflammatory and immunogenic phenotype to an anti-inflammatory and tolerogenic state. PRP6-HO7 lacks complement regulatory activity but retains full immunomodulatory activity over inflammatory Mo-DCs induced by TLRs, characterized by downregulation of relevant surface markers such as CD83, HLA-DR, co-stimulatory molecules such as CD86, CD80 and CD40, and pro-inflammatory cytokines such as IL-12 and TNF-alpha. Furthermore, PRP6-HO7-treated Mo-DCs shows increased endocytosis, significantly reduced CCR7 expression and CCL21-mediated chemotaxis, and prevents T cell alloproliferation. Finally, PRP6-HO7 shows also full immunomodulatory activity over Mo-DCs isolated from lupus nephritis patients with active disease, even without further pro-inflammatory stimulation. Therefore PRP6-HO7, retaining the immunomodulatory activity of C4BP(beta-) and lacking its complement regulatory activity, might represent a promising and novel alternative to treat autoimmune diseases. | - |
dc.format.extent | 16 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Frontiers Media | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2022.883743 | - |
dc.relation.ispartof | Frontiers in Immunology, 2022, vol. 13 | - |
dc.relation.uri | https://doi.org/10.3389/fimmu.2022.883743 | - |
dc.rights | cc by (c) Serrano, Inmaculada et al, 2022 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Immunoregulació | - |
dc.subject.classification | Lupus | - |
dc.subject.other | Immunoregulation | - |
dc.subject.other | Lupus | - |
dc.title | The Hidden Side of Complement Regulator C4BP: Dissection and Evaluation of Its Immunomodulatory Activity | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2022-05-26T09:45:35Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 35547734 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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fimmu-13-883743.pdf | 5.96 MB | Adobe PDF | View/Open |
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