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The Hidden Side of ...
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Serrano, InmaculadaBellvitge University Hospital-IDIBELL
(författare)
The Hidden Side of Complement Regulator C4BP : Dissection and Evaluation of Its Immunomodulatory Activity
- Artikel/kapitelEngelska2022
Förlag, utgivningsår, omfång ...
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2022-04-25
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Frontiers Media SA,2022
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:daa49fd6-b2c7-4a45-af27-870ce7227d84
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https://lup.lub.lu.se/record/daa49fd6-b2c7-4a45-af27-870ce7227d84URI
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https://doi.org/10.3389/fimmu.2022.883743DOI
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Språk:engelska
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Sammanfattning på:engelska
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Klassifikation
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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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(β-) isoform directly acting over inflammatory phagocytes. Here we show that incorporation of the β-chain to the C4BP α-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 α-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-α. 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(β-) and lacking its complement regulatory activity, might represent a promising and novel alternative to treat autoimmune diseases.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Luque, AnaBellvitge University Hospital-IDIBELL
(författare)
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Mitjavila, FrancescaBellvitge University Hospital-IDIBELL
(författare)
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Blom, Anna M.Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Department of Translational Medicine,Faculty of Medicine,Protein Chemistry, Malmö,Lund University Research Groups(Swepub:lu)klke-abl
(författare)
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Rodríguez de Córdoba, SantiagoCSIC Spanish National Research Council
(författare)
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Vega, M. CristinaCSIC Spanish National Research Council
(författare)
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Torras, JoanBellvitge University Hospital-IDIBELL
(författare)
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Aran, Josep M.Bellvitge University Hospital-IDIBELL
(författare)
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Bellvitge University Hospital-IDIBELLInstitutionen för translationell medicin
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Frontiers in Immunology: Frontiers Media SA131664-3224
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